You are here  > Biopharmaceutical Glossary Homepage > Concise pharmaceutical glossary & taxonomy

 Concise BioPharmaceutical Glossary & Taxonomy
Evolving Terminology for Emerging Technologies
Comments? Questions? Revisions?
Mary Chitty MSLS
Last revised July 12, 2019

About this glossary   Basic genetics & genomics: What's the difference?   Biopharmaceutical best practices, lessons learned & ongoing challenges

adverse drug reaction ADR:  ADRs may include drug interactions as one of many causes but the reverse is not true. The reader is cautioned regarding usage of drug reaction terms as multiple nearly- similar terms of varying granularity abound. .. "An adverse reaction to a drug has been defined as any noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment(2). However, WHO's original definition of ADR excluded therapeutic failures, intentional and accidental poisoning and drug abuse, as well as adverse events due to medication errors such as drug administration or non- compliance(1) ... Due to non- uniform usage of these terms, it is sometimes difficult to compare various studies and derive incidence rates, etc. for ADRs, and Drug Interactions. Saeed A Khan, "Drug Interaction or Adverse Drug Reaction? Confusing Terms", British Medical Journal 10 July, 1998  Alternatively: ADE Adverse Drug Event

adaptive clinical trials: The pharma industry is gradually coming to realize that the classically structured clinical trial does not offer enough flexibility to make use of continuously emerging knowledge that is generated as the trial progresses. Unacceptable levels of attrition in the clinical stage of development are driving profound changes in the architecture, design, and analysis of clinical trials. The majority of respondents to our survey said that reduction in patient numbers, less exposure to study drug, and drops in overall trial duration were key points in favor of adaptive designs; however, a majority also had specific concerns with adaptive trials―concerns that involved methodological, logistical, and regulatory uncertainties:   Herman Mucke, Adaptive Clinical Trials: Innovations in clinical trial design, management and analysis, Insight Pharma Reports, 2007

ADMET Administration, Dosage, Metabolism, Elimination, Toxicology:  We know a lot about A and M, not so much about D and E.  
Alternatively ADME/Tox.  Related terms: bioequivalence, drug disposition, pharmacodynamics, pharmacokinetics

AITrends: Business and Technology of Enterprise Artificial Intelligence

alternative splicing:   The production of two or more distinct mRNAs from RNA transcripts having the same sequence via differences in splicing (by the choice of different exons). Mouse Genome Informatics 

Recent genome- wide analyses of alternative splicing indicate that 40- 60% of human genes have alternative splice forms, suggesting that alternative splicing is one of the most significant components of the functional complexity of the human genome. Here we review these recent results from bioinformatics studies, assess their reliability and consider the impact of alternative splicing on biological functions. Although the 'big picture' of alternative splicing that is emerging from genomics is exciting, there are many challenges. High- throughput experimental verification of alternative splice forms, functional characterization, and regulation of alternative splicing are key directions for research. B. Modrek, C. Lee, "A genomic view of alternative splicing" Nature Genetics30 (1) :13- 19, Jan. 2002 

analyte specific reagents: antibodies, both polyclonal and monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reaction with substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens. CFR Title 21  Wikipedia     See also Laboratory Developed Tests

antisense (molecule): An oligonucleotide or analog thereof that is complementary to a segment of RNA or DNA and that binds to it and inhibits its normal function. IUPAC Medicinal Chemistry

Molecular biologists describing DNA sequences or referring to one of the two strands of double- stranded DNA frequently use complementary pairs of terms, such as coding/ non- coding, sense/ nonsense or transcribing/ non- transcribing. Unfortunately none of these pairs is defined in a universally accepted way…Of the three pairs of terms mentioned, NC- IUB and JCBN believe coding/ non- coding to be preferable. Moreover, as the word 'coding' refers to the relationship between nucleic acids and proteins, rather than the mere transcription of DNA into RNA, it is logical to call the strand with the mRNA sequence the coding strand, as in the first example. When DNA sequences are described by giving the sequence of only one strand, this is usually the strand with the same sequence as the RNA (messenger, ribosomal, transfer, etc.) and should therefore be called the coding strand. [JCBN/ NC- IUB Newsletter, Joint Commission on Biological Nomenclature and Nomenclature Commission of IUB 1989  Narrower terms: antisense DNA, antisense oligonucleotides, antisense RNA.  Related terms: RNAi; missense mutation, nonsense mutation; ribozymes

antisense DNA: DNA that is complementary to the sense strand. (The sense strand has the same sequence as the mRNA transcript. The antisense strand is the template for mRNA synthesis.) Synthetic antisense DNAs are used to hybridize to complementary sequences in target RNAs or DNAs to effect the functioning of specific genes for investigative or therapeutic purposes. MeSH, 1991  

antisense oligonucleotides: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize. MeSH, 1991

An oligonucleotide that has a complementary sequence to a portion of, or to all of, an mRNA. Being complementary to a particular target mRNA, antisense oligonucleotides bind specifically to that mRNA; the proprietary chemical modifications made to the antisense molecules facilitate tight binding. When binding occurs, the ability of the mRNA to be read by the cell’s translational machinery is inhibited, and synthesis of the protein that it encodes is blocked. Unlike a gene knockout, this inhibition requires the continuous presence of the antisense molecule; thus, it is reversible. A great advantage of antisense technology is that researchers can design specific inhibitors of a gene of interest based only on knowledge of the gene sequence.

apoptosis: One of the two mechanisms by which CELL DEATH occurs (the other being the pathological process of NECROSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and  appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA FRAGMENTATION) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. MeSH, 1993

If someone could figure out how to make fat cells undergo apoptosis (without harmful side effects) they could make a bundle. Related terms: programmed cell death

artificial intelligence (AI): Theory and development of COMPUTER SYSTEMS which perform tasks that normally require human intelligence. Such tasks may include speech recognition, LEARNING; VISUAL PERCEPTION; MATHEMATICAL COMPUTING; reasoning, PROBLEM SOLVING, DECISION-MAKING, and translation of language.  Year introduced: MeSH  1986

A wide- ranging term encompassing computer applications that have the ability to make decisions; the ability to explain reasoning is evidence of intelligence.  Also covers methods that have the ability to learn. J Glassey et al. “Issues in the development of an industrial bioprocess advisory system” Trends in Biotechnology 18 (4):136-41 April 2000

Or as some people have noted, laboriously trying to get computers to do what people do intuitively, without great effort. Conversely there are things computer can do (relatively) effortlessly such as massive numbers of  error- free calculations. The most promising applications seem to involve incorporating both computer aided consideration of many possibilities, combined with human judgment.  Narrower terms: artificial general intelligence, artificial narrow intelligence, cellular automata, expert systems, fuzzy logic, genetic algorithms, neural nets Related terms: augmented intelligence, training sets. 

attrition  Early attrition of poor drug candidates is central to the new drug discovery paradigm. Better to kill compounds before moving them into expensive clinical trials.  

augmented intelligence: As artificial intelligence (AI) grows more powerful, it can enable new solutions to these systemic [health] issues. … Better described as augmented intelligence, AI uses machine learning to rapidly analyze a range of environmental, behavioral and clinical data to generate insights. By using computational neural networks, it will someday be possible to use big data to quickly identify causal linkages between specific evidence-based treatments and improved patient outcomes. Nearer term, AI has a critical role to play in improving the efficiency of health care delivery and drug development. … by mining large volumes of clinical data quickly, AI can also help physicians make better evidence-based treatment decisions, especially in therapy areas where the standard of care is changing rapidly.  Meanwhile, for the life sciences industry AI’s main draw is its potential to tackle ongoing R&D productivity challenges. AI analytics and predictive simulations can improve the drug development failure rate by offering an in silico screen to better understand which targeted interventions are likely to succeed or fail. By narrowing the funnel of drug candidates earlier, companies can begin to streamline research costs, while biasing human studies for success. AI can also improve the efficiency of clinical trials, enabling more targeted patient recruitment to reduce enrolment times, and, through adaptive behavioral analytics, increasing both patient compliance and retention. EY, What’s the right dose of AI to revitalize healthcare?

Bayesian statistics: Bayesian statistics is an approach for learning from evidence as it accumulates. In clinical trials, traditional (frequentist) statistical methods may use information from previous studies only at the design stage. Then, at the data analysis stage, the information from these studies is considered as a complement to, but not part of, the formal analysis. In contrast, the Bayesian approach uses Bayes’ Theorem to formally combine prior information with current information on a quantity of interest. The Bayesian idea is to consider the prior information and the trial results as part of a continual data stream, in which inferences are being updated each time new data become available. Throughout this document we will use the terms “prior distribution”, “prior probabilities”, or simply “prior” to refer to the mathematical entity (the probability distribution) that is used in these Bayesian calculations. The term “prior information” refers to the set of all information that may be used to construct the prior distribution. FDA, CBER, CDHR Guidance for the use of Bayesian Statistics in Medical Device Clinical Trials Feb. 2010

big pharmas: MedAdNews publishes an annual list of the top 50 pharmaceutical companies each fall. "Biotech" companies such as Amgen are bigger than some pharmas.

biobank: A type of biorepository that stores biological samples (usually human) for use in research Wikipedia

bioelectronics: the field of developing medicines that use electrical impulses to modulate the body's neural circuits. Virtually all of the body's organs and functions are regulated through circuits of neurons communicating through electrical impulses. The theory is that if you can accurately map the neural signatures of certain diseases, you could then stimulate or inhibit the malfunctioning pathways with tiny electrodes in order to restore health, without having to flood the system with molecular medicines. Electroceuticals swapping drugs for devices, Wired 28 May 2013  Related term: electroceuticals; Genomics optogenetics

bioengineering:  The application of a systematic, quantitative, and integrative way of thinking about and approaching the solutions of problems important to biology, medical research, clinical proactive, and population studies. The NIH Bioengineering Consortium agreed on the following definition for bioengineering research on biology, medicine, behavior, or health recognizing that no definition could completely eliminate overlap with other research disciplines or preclude variations in interpretation by different individuals and organizations. Integrates physical, chemical, or mathematical sciences and engineering principles for the study of biology, medicine, behavior, or health. It advances fundamental concepts, creates knowledge for the molecular to the organ systems levels, and develops innovative biologics, materials, processes, implants, devices, and informatics approaches for the prevention, diagnosis, and treatment of disease, for patient rehabilitation, and for improving health.!po=12.5000 

bioinformatics:  Roughly, bioinformatics describes any use of computers to handle biological information. In practice the definition used by most people is narrower; bioinformatics to them is a synonym for "computational molecular biology" - the use of computers to characterise the molecular components of living things. [Damian Counsell, FAQ] See for tight and loose definitions of bioinformatics, and information on how long the term has been used. Research, development or application of computational tools and approaches for expanding the use of biological, medical, behavioral or health data, including those to acquire, store, organize, archive, analyze, or visualize such data. Biomedical Information Science and Technology Initiative BISTI Bioinformatics at the NIH, 2000 

We have coined the term Bioinformatics for the study of informatic processes in biotic systems. Our Bioinformatic approach typically involves spatial, multi- leveled models with many interacting entities whose behavior is determined by local information. Theoretical Biology Group, Univ. of Utrecht, Netherlands, Paulien Hogeweg Director

Original definition was “the study of informatic processes in biotic systems” Paulien Hogeweg MIRROR beyond MIRROR, puddles of LIFE, in Artificial Life, ed. C.G. Langton, Addison Wesley, 297-316, 1988 [Nick Saville's homepage, Theoretical Biology and Bioinformatics, Utrecht Univ., Netherlands, 1997   Alternatively computational biology

biologics: Biologics, in contrast to drugs that are chemically synthesized, are derived from living sources (such as humans, animals, and microorganisms). Most biologics are complex mixtures that are not easily identified or characterized, and many biologics are manufactured using biotechnology. Biological products often represent the cutting- edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available.  About CBER, FDA, US

 Includes blood, vaccines, tissue, allergenics and biological therapeutics.
   See also biological products, biopharmaceutical

biological markers:   Measurable and quantifiable biological parameters (e.g. specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health - and physiology related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. MeSH, 1989 

1. Parameter that can be used to identify a toxic effect in an individual organism and can be used in extrapolation between species. 2. Indicator signalling an event or condition in a biological system or sample and giving a measure of exposure, effect, or susceptibility.  IUPAC Tox
Alternatively/Related/synonymous? terms: biomarkers, genetic markers, surrogate markers; Broader term: markers  Narrower term: genomic biomarkers

biological products: Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. The Center for Biologics Evaluation and Research (CBER) is responsible for ensuring the safety and efficacy of the biological products.  See also biologics, biopharmaceutical

biomarker guidelines: The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and Drug Administration (FDA) guidance documents, and conducted a survey of investigators to determine practices and challenges to executing biomarker studies in clinical trials of new drugs in early development. This document provides standard definitions and categories of biomarkers, and lists recommendations to sponsors and investigators for biomarker incorporation into such trials. Our recommendations for sponsors focus on the identification and prioritization of biomarkers and assays, the coordination of activities for the development and use of assays, and for operational activities. We also provide recommendations for investigators developing clinical trials with biomarker studies for scientific rationale, assay criteria, trial design, and analysis. Guidelines for the Development and Incorporation of Biomarker Studies in Early Clinical Trials of Novel Agents,  Dancey JE, et. al,  Clin Cancer Res. 2010 Mar 9. [Epub ahead of print]

biomarker/s: The term “biomarker”, a portmanteau of “biological marker”, refers to a broad subcategory of medical signs – that is, objective indications of medical state observed from outside the patient – which can be measured accurately and reproducibly. Medical signs stand in contrast to medical symptoms, which are limited to those indications of health or illness perceived by patients themselves. There are several more precise definitions of biomarkers in the literature, and they fortunately overlap considerably. In 1998, the National Institutes of Health Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. What are Biomarkers? Kyle Strimbu and Jorge A. Tavel, M.D. Curr Opin HIV AIDS. Nov 2010; 5(6): 463–466.doi:  10.1097/COH.0b013e32833ed177   

biomathematics: The application of mathematics to problems in biology and medicine. An essential tool in fields such as population genetics, cellular neurobiology, comparative genetics, biomedical imaging, pharmacokinetics, and epidemiology. It plays an increasingly vital role in the effort to understand diseases and disorders, and to improve therapies.  Collection Development Manual, National Library of Medicine, US 2004 

BioMEMS Biological MicroElectro Mechanical Systems: Includes micro & nano drug delivery, interface of nanoscience and tissue engineering, microfluidics, and miniaturized total analysis systems (microTAS), biosensors, innovations in mass spectrometry, and nanoscale imaging.  

biomimetics: An interdisciplinary field in materials science, ENGINEERING, and BIOLOGY, studying the use of biological principles for synthesis or fabrication of BIOMIMETIC MATERIALS. MeSH 2003

There is a need to develop the next generation of restorative materials and medical implants. New avenues of scientific inquiry may enable the development of biomaterials that are safe, reliable, "smart", long- lasting, and perform ideally in their respective biological environments. ... Over the last few years biomimetics and tissue engineering have emerged as a new vision in the field of tissue and organ repair and restoration. Biomimetics and tissue engineering are interdisciplinary fields that combine information from the study of biological structures and their functions with physics, mathematics, chemistry and engineering for the generation of new materials, tissues and organs. These approaches can offer new ways of: (a) developing biological solutions for future design and synthesis of composite materials such as bone, cartilage, tendon, ligament, skin, dentin, enamel, cementum and periodontal ligament; (b) replacing and assembling functional tissues and organs; and (c) evaluating medical and dental implants. In the area of craniofacial, oral and dental principles from biomimetics and tissue engineering are applied to developing dental and facial implants, new polymers for guided tissue regeneration used in treating periodontal disease and bone and connective tissue defects, coral- based hydroxyapatite replicas for reconstruction of alveolar ridges and other osseous defects, temporomandibular joint (TMJ) and other joint prostheses, formation of bone matrix substitutes, and artificial replicas of bone, skin, and mucosa.  [National Institute of Dental Research, NIH, US, Biomimetics and Tissue Engineering in the Restoration of Orofacial Tissues, RFA: DE-98-009, June 19, 1998]

biomolecular materials:  The major program emphasis is the creation of robust, scalable, energy-relevant materials and systems with emergent behavior that work with the extraordinary effectiveness of molecules and processes of the biological world. Major thrust areas include: understanding, controlling, and building complex hierarchical structures by mimicking nature’s self- and directed-assembly approaches; design and synthesis of environmentally adaptive, self-healing multi-component, e.g., inorganic, polymeric, and biological, materials and systems that demonstrate energy conversion and storage capabilities found in nature; functional systems with collective properties not achievable by simply summing the individual components; biomimetic and/or bioinspired routes for the synthesis of energy relevant materials, e.g., semiconductor and magnetic materials under mild conditions; and development of science-driven tools and techniques for the characterization of biomolecular and soft materials.

biomolecular screening:   The term "biomolecular screening" became widely used in the late 1980's to broadly describe a new and rapidly adopted process for lead identification in drug discovery.  This new process involved screening natural product extracts and/or amassed compound collections, typically from pharmaceutical companies, in a random, unbiased manner to identify novel modulators of biological targets ... The screens encompassed bioassays that could be cell-based or purely biochemical in nature, and the need to screen increasing numbers of samples as time progressed, fostered the development of many new assay formats. IUPAC Glossary of terms in Biomolecular Screening 2011

An organic molecule, part of a living organism. Includes proteins, DNA, RNA

biopharmaceutical:  also known as a biologic(al) medical productbiological,[1] or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccinesblood, blood components, allergenicssomatic cellsgene therapiestissuesrecombinant therapeutic protein, and living cells used in cell therapy. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living cells or tissues. They (or their precursors or components) are isolated from living sources—human, animal, plant, fungal, or microbial.

Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. Some regulatory agencies use the terms biological medicinal products or therapeutic biological product to refer specifically to engineered macromolecular products like protein- and nucleic acid-based drugs, distinguishing them from products like blood, blood components, or vaccines, which are usually extracted directly from a biological source.[2][3][4] Specialty drugs, a recent classification of pharmaceuticals, are high-cost drugs that are often biologics.[5][6][7] The European Medicines Agency uses the term advanced therapy medicinal products (ATMPs) for medicines for human use that are "based on genes, cells, or tissue engineering",[8] including gene therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines, and combinations thereof.[9] Within EMA contexts, the term advanced therapies refers specifically to ATMPs, although that term is rather nonspecific outside those contexts. Wikipedia accessed 2018 March 1

See also biologics, biological products

biopolymers: Macromolecules (including proteins, nucleic acids and polysaccharides) formed by living organisms. IUPAC Compendium  Broader term: polymers

bioprinting: A material transfer technique used for assembling biological material or cells into a prescribed organization to create functional structures such as MICROCHIP ANALYTICAL DEVICES, cell microarrays, or three dimensional anatomical structures. MeSH 2013

New manufacturing technologies under the banner of rapid prototyping enable the fabrication of structures close in architecture to biological tissue. In their simplest form, these technologies allow the manufacture of scaffolds upon which cells can grow for later implantation into the body. A more exciting prospect is the printing and patterning in three dimensions of all the components that make up a tissue (cells and matrix materials) to generate structures analogous to tissues; this has been termed bioprinting.  Printing and prototyping of tissues and scaffolds. Derby B. Science. 2012 Nov 16;338(6109):921-6. doi: 10.1126/science.1226340 

biorobotics:   Our research focuses on the role of sensing and mechanical design in motor control, in both robots and humans. This work draws upon diverse disciplines, including biomechanics, systems analysis, and neurophysiology. The main approach is experimental, although analysis and simulation play important parts.  In conjunction with industrial partners, we are developing applications of this research in biomedical instrumentation, teleoperated robots, and intelligent sensors. Harvard Biorobotics Laboratory 

biotechnology: The integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof  and molecular analogues for products and services. IUPAC Compendium 

biotechnology firms: The congressional Office of Technology concluded in its pathbreaking 1984 report, and emphasized even more strongly in another 1991 report, that "biotechnology" is not an industrial sector, but rather a set of methods useful in many industrial sectors (usually established ones such as drugs and biologics, devices, or agriculture), but also for some entirely new applications (e.g., DNA forensics). Many firms, almost 1500 listed by the various online services, are called "biotechnology" firms because they are largely built around technologies developed since 1980. These firms are generally competing in established markets, however, even when they compete by using novel products, services, and technical approaches. Robert Cooke- Deegan et. al., World Survey of Funding for Genomics Research: Final Report to the Global Forum for Health Research and the World Health Organization,  September 2000 

biotechnology industry:  The biotechnological innovations of the 1970’s took until the 1990’s to integrate.  "The Pharmaceutical Industry and the Revolution in Molecular Biology: Exploring the Interactions between Scientific, Institutional and Organizational Change, Iain M. Cockburn, Rebecca Henderson, Scott Stern, 1999.  
Integration of genomics (and proteomics) into drug discovery and development seems likely to be an ongoing process as well. 

Biotechnology started as a means for producing biopharmaceuticals.  It has only relatively recently begun to be more integrated into the drug discovery and development process.

blockbuster drugs: an extremely popular drug that generates annual sales of at least $1 billion for the company that sells it. Examples of blockbuster drugs include Vioxx, Lipitor and Zoloft.

90% of drugs marketed by big pharma bring in less than $180 million per year. Compare that number to the total cost of $350- 600 million for approving a single drug (including all the failures that lead up to it). Of course, one might think that the money can be made back in four years, but drugs have a huge maintenance cost in terms of regulatory compliance, marketing and sales. The margin on a drug- to- drug basis is very slim. This places the onus on the other 10% of drugs to be blockbusters – to more than make up for most of the other drugs that are earning far too little revenue. This is how the industry has structured itself around a blockbuster mentality – a reliance on drugs that bring in at least $500 million per year in revenue. Considering the odds of achieving blockbuster status, this is a very high- risk strategy. Pharmaceutical companies will have to change their ways if they are going to enter the new era of individualized medicine. 
Related terms: FIPCO, franchises- pharmaceutical, market fragmentation, multibusters,  pharmaceutical industry

borderline products:  Sometimes it may be unclear whether a particular product is a cosmetic product under cosmetics legislation or whether it falls under other sectorial legislation. In the case of these “borderline products”, the decision on a product’s classification must be taken on a case-by-case basis.  European Commission, Cosmetics 

bottom up: The classical reductionist approach to biology which aims to examine the smallest units to gain insight into the larger ones. Mendelian genetics, which looks at single genes, is a bottom- up approach.   Compare top- down 

brand name drug: A drug marketed under a proprietary, trademark- protected name. Glossary, Drugs@FDA, CDER,   

Related terms: proprietary drug, proprietary name

cancer genome interpretation: Much promise exists in cancer precision medicine, in which the identification of the specific mutations in a patient’s tumor allow doctors to tailor appropriate treatments for individual patients. Unfortunately, cancer precision medicine is not yet a reality for most cancer patients, because we cannot fully interpret the clinical impact of the cancer genome. Broad Institute 

CAR T-cell therapyA type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is being studied in the treatment of some types of cancer. Also called chimeric antigen receptor T-cell therapy. NCI Dictionary of Cancer Terms

CBER Center for Biologics Evaluation and Research: CBER is the Center within FDA that regulates biological products for human use under applicable federal laws, including the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them.

CDER Center for Drug Evaluation and Research:  The Center for Drug Evaluation and Research (CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the health of people in the United States.  As part of the U.S. Food and Drug Administration (FDA), CDER regulates over-the-counter and prescription drugs, including biological therapeutics and generic drugs. This work covers more than just medicines. For example, fluoride toothpaste, antiperspirants, dandruff shampoos and sunscreens are all considered "drugs."

cDNA complementary DNA: A single stranded DNA molecule with a nucleotide sequence that is complementary to an RNA molecule; cDNA is formed by the action of the enzyme reverse transcriptase on an RNA template. After conversion to the double stranded form, cDNA is used for molecular cloning or for hybridization studies. [IUPAC Biotech]

A complementary DNA for a messenger RNA molecule. Unlike an mRNA, a cDNA can be easily propagated and sequenced. [NCBI] 

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA- dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not cDNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe. MeSH, 1994

chaperome: The goal of the "All Chaperome" project is to characterize the molecular chaperones of C. elegans. We have identified approximately 170 chaperones corresponding to the major classes of chaperones and co-chaperones conserved in S. cerevisiae, and vertebrates.  Taking advantage of the lineage analysis of C. elegans, we are determining the expression pattern of each chaperone gene to establish a basis for network interactions and tissue specificity during development and aging.  Morimoto Laboratory, All Chaperome Project, 2007 Thanks to Heike Aßmus, University of Rostock for alerting me to this -ome. 

checkpoint inhibitors: Most of the current excitement over cancer immunotherapy is focused on the field of immune checkpoint inhibitors, a class of monoclonal antibodies (MAbs) that inhibit pathways that block the response of T cells to antigens. Checkpoint inhibitors work to overcome mechanisms by which tumors co-opt certain immune checkpoint pathways, and thus resist T cell-mediated antitumor immunity. Cancer Immunotherapy: Immune Checkpoint Inhibitors, Cancer Vaccines, and Adoptive T-cell Therapies report, 2014  

chemical genetics: A "chemistry first" approach to drug discovery. Chemical genetics strategies start with libraries of chemical compounds, and then screen these libraries to find compounds that produce differences in a disease- relevant phenotype. Once a phenotype modifying compound is found, it is used to identify the particular target protein to which it binds in the cells or small model organisms in which it had previously been studied.  Sometimes used interchangeably with "chemical genomics". 

"Chemical genetics approach" first coined [by Rebecca Ward, at Harvard University] on the inaugural cover of Chemistry and Biology nine years ago. Her term reminds us that to understand a life process you should perturb it and determine the consequence and that such an approach should strive to have the broad power and generality of  genetics. Stuart L. Schreiber, The Small Molecule Approach to Biology, Chemical & Engineering News, March 3, 2003  Alternatively/Related terms: biochemical genomics, chemical genomics, chemogenomics, chemical proteomics

chemical information: Many people view chemoinformatics as an extension of chemical information, which is a well established concept covering many areas that employ chemical structures, data storage and computational methods, such as compound registration databases, on- line chemical literature, SAR analysis and molecule- property calculation. Timothy Ritchie "Chemoinformatics; manipulating chemical information to facilitate decision- making in drug discovery" Drug Discovery Today 6(16): 813-814, Aug. 2001

chemical information system: Must include registration, computed and measured properties, chemical descriptors and inventory. The primary purpose is to be able to identify a chemical substance, find compounds similar to the target compound and determine the location of the compound. To effectively build it, an object definition of the chemical sample is paramount…The hub [central database] of the chemical information system is the inventory system. Frank Brown "Chemoinformatics: What is it and How does it Impact Drug Discovery" Annual Reports in Medicinal Chemistry 33: 375-384, 1998

cheminformatics: The practice of  finding the "best- fitting" compounds to address particular targets. The field encompasses diversity analysis and library design, virtual screening, rational drug design, and tools and approaches for predicting activity and other properties from structure. Going by the numbers in cheminformatics seems to be the currently most used form of this word, overtaking chemoinformatics in about 2001.  Alternatively chemical informatics, chemical information, chemi-informatics

chemoinformatics:  Chemoinformatics is an integral part of the discipline of knowledge management.  Nicholas J. Hrib, Norton P. Peet "Chemoinformatics: are we exploiting these new science?" Drug Discovery Today 5 (11): 483- 485, Nov. 2000

Increasingly incorporates "compound registration into databases, including library enumeration; access to primary and secondary scientific literature; QSAR Quantitative Structure Activity Relationships) and similar tools for relating activity to structure; physical and chemical property calculations; chemical structure and property databases, chemical library design and analysis; structure- based design and statistical methods. Because these techniques have traditionally been considered the realms of scientists from different disciplines, differences in computer systems and terminology provide a barrier to effective communication. This is probably the single most challenging problem that chemoinformatics must solve. [M Hann and R Green "Chemoinformatics – a new name for an old problem?" Current Opinion in Chemical Biology 3:379- 383, 1999]

Mixing of information technology and management to transform data into information and information into knowledge for the intended purpose of making better decisions faster in the arena of drug lead identification and optimization. ..In Chemoinformatics there are really only two [primary] questions: 1.) what to test next and 2.) what to make next. The main processes within drug discovery are lead identification, where a lead is something that has activity in the low micromolar range, and lead optimization, which is the process of transforming a lead into a drug candidate. [Frank Brown  "Chemoinformatics: What is it and How does it Impact Drug Discovery" Annual Reports in Medicinal Chemistry 33: 375-384, 1998

chemotherapy: Often refers to cancer treatments, but is also used more generally for drug therapy.  Wikipedia  
Synonyms: Drug treatment (drug therapy), medication therapy, pharmacotherapeutics, pharmacotherapy 
Genetics Home Reference, National Library of Medicine, NIH 

circulating tumor cells CTCs: Molecular characterization of tumour material will become increasingly important in selecting patients for clinical trials and offering appropriate treatment for patients in clinical practice. Recent advances in the field have indicated that the molecular characteristics of a tumour can be determined from circulating tumour cells and circulating tumour DNA; thus, a simple blood sample could provide these data in a simple, convenient and efficient manner. Circulating tumour-derived predictive biomarkers in oncology, Hodgson DR, Wellings R, Orr MC, McCormack R, Malone M, Board RE, Cantarini MV., AstraZeneca, Drug Discovery Today. 2010 Feb;15(3-4):98-101. Epub 2010 Jan 4.

clinical bioinformatics: Different from other informatics, clinical bioinformatics should focus more on clinical informatics, including patient complaints, history, therapies, clinical symptoms and signs, physician's examinations, biochemical analyses, imaging profiles, pathologies and other measurements. It was emphasized that the simultaneous evaluation of clinical and basic research could improve medical care, care provision data, and data exploitation methods in disease therapy and algorithms for the analysis of such heterogeneous data sets.  Clinical bioinformatics: a new emerging science Xiangdong Wang and Lance Liotta, Journal of Clinical Bioinformatics 1:1 2011 pmc/articles/PMC3097094/

clinical informatics: The application of informatics approaches to the clinical- evaluation phase of drug development. These approaches can include clinical- trial simulations to improve trial design and patient selection, as well as electronic capturing and storing of clinical data and protocols. The goal is to reduce expenses and time to market   
Clinical Informatics New

clinical trials:
Pharmacogenomics is a key tool for the design and interpretation of clinical trials. It contributes to a precise definition of a disease. It has the ability to correlate drug response to genetic markers and predict dose response and adverse events in some cases. It allows for representative subject populations within the clinical trial, and it allows for the stratification of patient populations. The potential benefits of that include reduction of drug development time due to the demonstration of efficacy in specific populations; the optimization of clinical utility by linking sub- types and efficacy; and reduction of time to market. Other potential benefits include the ability to differentiate between responder and non- responder populations, which may lead to a greater likelihood of reimbursement in the end.

clinical proteomics: Aims to discovery proteins with medical relevance said Alan Sachs, a director of R&D at Merck. Such discoveries can be defined broadly as those that identify a potential target for pharmaceutical development, a marker(s) for disease diagnosis or staging and risk assessment, both for medical and environmental studies. (Note that there is a difference between developing biological insight and identifying clinically important diagnostic and prognostic protein- based assays.) Defining the Mandate of Proteomics in the Post- Genomics Era, Board on International Scientific Organizations, National Academy of Sciences, 2002

clone:  A population of genetically identical  cells produced from a common ancestor. Sometimes also used to refer to a number of recombinant DNA molecules all carrying the same inserted sequence. IUPAC Medicinal Chemistry, IUPAC Compendium 

Clone was coined by Herbert J. Webber in 1903 for "a colony of organisms derived asexually from a single progenitor" and was quickly adopted by botanists and cell biologists. But the popular perception of cloning can be traced to Alvin Toffler's Future Shock (1970) and was quickly popularized (and extended to items such as computers). But Lee Silver, Professor of Molecular Biology and Public Affairs, Princeton Univ. concludes that "the scientific community has lost control over Webber's pleasant sounding little word. Cloning has a popular connotation that is impossible to dislodge. We must accept that democratic debate on cloning is bereft of any meaning. Science and Scientists would be better served by choosing other words to explain advances in developmental biotechnology to the public". L. Silver "What are clones? They're not what you think they are" Nature 412 (6842): 21, 5 July 2001

cloning:  Using specialized DNA technology (see cloning vector) to produce multiple, exact copies of a single gene or other segment of DNA to obtain enough material for further study. This process is used by researchers in the Human Genome Project, and is referred to as cloning DNA. The resulting cloned (copied) collections of  DNA molecules are called clone libraries. A second type of cloning exploits the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell. A third type of cloning produces complete, genetically identical animals such as the famous  Scottish sheep, Dolly.  DOE

The process of making copies of a specific piece of DNA, usually a gene. When geneticists speak of cloning, they do not mean the process of making genetically identical copies of an entire organism. NHGRI

Rooting plant cuttings and having identical twins can also be considered types of cloning.

collaboration: Collaboration can be horizontal (a group of small companies), vertical (suppliers and customers), sectoral (same industry sector) or lateral (complementary but different sectors). From the Latin, meaning to work with. 

The biomedical industry faces a crisis in productivity, with rapidly rising costs for R&D but declining results. While many other industries have found ways to enhance performance using pre-competitive collaboration, the biomedical industry has been reluctant to embrace such sharing of information, investments, risk and costs. There are, however, encouraging signs that important shifts are taking place, as evidenced by a growing number of consortia, programs for open innovation, and experiments with crowd-sourcing to find solutions outside a single company. One area ripe for collaboration is the field of neglected diseases, where the shortage of traditional profit opportunities mean that companies are forced to re-think how to achieve the most productive results.

combination products: Include (1) A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity; (2) Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products; (3) A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or (4) Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect. Definition of a Combination Product, FDA, Office of Combination Products, As defined in 21 CFR § 3.2(e)

combination therapies: As ever more combination therapies are applied in various areas of medicine, there is a growing need for quantitative descriptions of combination effects. While most of the scientific community has agreed on a basic standard for synergy, there is no consensus on quantifying the degree to which a combination may deviate from synergy, and no predictive models are accepted to serve as benchmarks.  This project will convene a working group, involving leading experts on combination effects, to (1) endorse the synergy criterion recommended at a recent meeting in Finland, (2) adopt standard measures of combination effect to quantify deviations from synergy, and (3) explore predictive combination-effect models for multiply-inhibited biological interaction networks. Quantifying the Effects of Compound Combinations Chemistry International 25 (4) July-Aug. 2004,

combinatorial chemistry:  Using a combinatorial process to prepare sets of  compounds from sets of  building blocks. IUPAC Combinatorial Chemistry   Related terms: combinatorial libraries, diversity, microtiter plates, molecular diversity, fully combinatorial, pool/ split

companion diagnostics: A trend in genetic diagnostics and therapeutics is for the two to become increasingly intertwined.  Companion diagnostics identify subsets of patients who would benefit from a specific drug. 

comparative effectiveness research CER:  the direct comparison of existing health care interventions to determine which work best for which patients and which pose the greatest benefits and harms. The core question of comparative effectiveness research is which treatment works best, for whom, and under what circumstances.[1]  The Institute of Medicine committee has defined CER as "the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels."[2] Comparative effectiveness research adopts many of the same approaches and methodologies as cost-effectiveness analysis, including the use of incremental cost-effectiveness ratios (ICERs) and quality-adjusted life years (QALYs). An important component of CER is the concept of pragmatic randomised controlled trials.[3] These clinical research trials measure the benefit produced by the treatment in routine clinical practice.  Wikipedia accessed 2018 Feb 26

complex: It has become common to use complicated and complex interchangeably … The essence of ‘complicated’ is hard to figure out. ..Complex, on the other hand is a term reserved for systems that display properties that are not predictable from a complete description of their components, and that are generally considered to be qualitatively different from the sum of their parts. [Editorial, "Complicated is not complex" Nature Biotechnology 17: 511 June 1999

Would it be fair to say that Mendelian genetics is linear, while genomics and polygenic diseases/traits are nonlinear?

According to the Oxford English Dictionary one of the meanings of complicated is complex, though it also means not easy to unravel or separate. Both complex and complicated are contrasted with simple. Whatever the original senses of these two words, the above distinction seems a useful one now.  Related term: complexity; Narrower terms: biocomplexity, complex diseases, complex genomes; complex phenotypes, complex traits  

complex diseases: Diseases characterized by risk to relatives of an affected individual which is greater than the incidence of the disorder in the population.[NHLBI

Are complex diseases essentially the same as polygenic diseases?

complex phenotypes: Those that exhibit familial clustering, which may mean that there is some genetic component, but that do not occur in Mendelian proportions in pedigrees. Complex phenotypes may be continuous in distribution, like height or blood pressure, or they may be dichotomous, like affected and not affected. The complexity arises from the fact one cannot accurately predict the expression of the phenotype from knowledge of the individual effects of individual factors considered alone, no matter how well understood each separate component may be. Genetic Architecture, Biological Variation and Complex Phenotypes, PA-02-110, May 29, 2002- June 5, 2005

complex trait: Has a genetic component that is not strictly Mendelian (dominant, recessive, or sex linked) and may involve the interaction of two or more genes to produce a phenotype, or may involve gene environment interactions." NHLBI  Related term: genetic architecture 

complexity:: Currently there are more than 30 different mathematical descriptions of complexity. However we have yet to understand the mathematical dependency relating the number of genes with organism complexity. J. Craig Venter et. al. "The sequence of the Human Genome" Science 291 (5507): 1347, Feb. 16, 2001 

An ill- defined term that means many things to many people. Complex things are neither random nor regular, but hover somewhere in between. Intuitively, complexity is a measure of  how interesting something is. Other types of complexity may be well defined. Gary William Flake, Computational Beauty of Nature: Computer Explorations of Fractals, Chaos, Complex Systems, and Adaptation, MIT Press, 1998 

compound quality: Physicochemical properties such as lipophilicity and molecular mass are known to have an important influence on the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of small-molecule drug candidates. To assess the use of this knowledge in reducing the likelihood of compound related attrition, the molecular properties of compounds acting at specific drug targets described in patents from leading pharmaceutical companies during the 2000-2010 period were analysed. ...  we conclude that a substantial sector of the pharmaceutical industry has not modified its drug design practices and is still producing compounds with suboptimal physicochemical profiles. Paul D. Leeson and Stephen A St-Gallay The influence of the "organizational factor" on compound quality in drug discovery, Nature Reviews Drug Discovery, 10:749-765, October 2011   
Figures and tables 

Computer-aided detection (CADe), also called computer-aided diagnosis (CADx), are systems that assist doctors in the interpretation of medical images. Imaging techniques in X-ray, MRI, and ultrasound diagnostics yield a great deal of information that the radiologist or other medical professional has to analyze and evaluate comprehensively in a short time. CAD systems process digital images for typical appearances and to highlight conspicuous sections, such as possible diseases, in order to offer input to support a decision taken by the professional.  CAD also has potential future applications in digital pathology with the advent of whole-slide imaging and machine learning algorithms. So far its application has been limited to quantifying immunostaining but is also being investigated for the standard H&E stain.[1]  CAD is an interdisciplinary technology combining elements of artificial intelligence and computer vision with radiological and pathology image processing. A typical application is the detection of a tumor. For instance, some hospitals use CAD to support preventive medical check-ups in mammography (diagnosis of breast cancer), the detection of polyps in the colon and lung cancer. Wikipedia accessed 2018 Feb 26

computational physiology: The International Union of Physiological Sciences (IUPS) Physiome Project is an internationally collaborative open- source project to provide a public domain framework for computational physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales [1,2,3]. It aims to develop an infrastructure for linking models of biological structure and function across multiple levels of spatial organization and multiple time scales. The levels of biological organisation, from genes to the whole organism, includes gene regulatory networks, protein- protein and protein- ligand interactions, protein pathways, integrative cell function, tissue and whole heart structure- function relations. The whole heart models include the spatial distribution of protein expression. Keynote: Peter J. Hunter, Univ of Auckland, International Society of Computational Biology, Detroit, MI, 2005 

Copy Number Polymorphisms CNPs:  represent a greatly underestimated aspect of human genetic variation. Recently, two landmark studies reported genome-wide analyses of CNPs in normal individuals and represent the beginning of an understanding of this type of large-scale variation.   Patrick G. Buckley*, Kiran K. Mantripragada*, Arkadiusz Piotrowski, Teresita Diaz de Ståhl and Jan P. Dumanski Copy-number polymorphisms: mining the tip of an iceberg, Trends in Genetics 21 (6): 315- 317, June 2005    Another term for CNV

Copy Number Variation CNV: We defined a CNV as a DNA segment that is 1kb or larger and present at variable copy number in comparison with a reference genome. A CNV can be simple in structure, such as tandem duplication, or may involve complex gains or losses of homologus sequences at multiple sites in the genome. Richard Redon et. al, Global Variaiton in copy number in the human genome, Nature 2006 Nov 23;444 (7118): 444- 454   

Copy number variations (CNVs) hold immense potential to explain genetic diversity, predict disease risk and diagnose complex genomic disorders have long resisted understanding. Now recently developed whole-genome scanning technologies have catalyzed the appreciation of CNVs in the genomic community. Studies linking insertions, deletions, and inversions to disease etiology continue to multiply. As genome-wide scanning techniques become more prevalent in diagnostic laboratories, the major challenge is how to interpret accurately which variations are pathogenic in nature and which are benign.  Related terms: SNP, HapMap

CRISPR: “CRISPR” (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defense system that forms the basis for CRISPR-Cas9 genome editing technology. In the field of genome engineering, the term “CRISPR” or “CRISPR-Cas9” is often used loosely to refer to the various CRISPR-Cas9 and -CPF1, (and other) systems that can be programmed to target specific stretches of genetic code and to edit DNA at precise locations, as well as for other purposes, such as for new diagnostic tools. With these systems, researchers can permanently modify genes in living cells and organisms and, in the future, may make it possible to correct mutations at precise locations in the human genome in order to treat genetic causes of disease. Other systems are now available, such as CRISPR-Cas13’s, that target RNA provide alternate avenues for use, and with unique characteristics that have been leveraged for sensitive diagnostic tools, such as SHERLOCK. Questions & Answers about CRISPR: What is CRISPR? , Broad Institute

Wikipedia  Related terms: gene editing, genome editing

CRISPR for Precision Medicine Developing Accuracy, Speed and Efficiency in Gene Editing and Repair MARCH 14-15, 2019 San Francisco CA Gene editing, particularly using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, has very rapidly established itself as an important tool in drug discovery and is now being exploited for therapeutic purposes as well.

CRISPR/Cas9: Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and RISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.  What are genome editing and CRISPR-Cas9?  Genetics Home Reference, NIH NLM 

CRISPR-Cas Systems: Adaptive antiviral defense mechanisms, in archaea and bacteria, based on DNA repeat arrays called CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS (CRISPR elements) that function in conjunction with CRISPR-ASSOCIATED PROTEINS (Cas proteins). Several types have been distinguished, including Type I, Type II, and Type III, based on signature motifs of CRISPR-ASSOCIATED PROTEINS. MeSH Year introduced: 2014 This comes under Gene Silencing, which comes under Gene Expression Regulation

data lake: The idea of data lake is to have a single store of all data in the enterprise ranging from raw data (which implies exact copy of source system data) to transformed data which is used for various tasks including reporting, visualization, analytics and machine learning. The data lake includes structured data from relational databases (rows and columns), semi-structured data (CSV, logs, XML, JSON) unstructured data (emails, documents, PDFs) and even binary data (images, audio, video) thus creating a centralized data store accommodating all forms of data. Wikipedia Accessed June 2017
Data Lake or data swamp, 2016

data quality:  A vital consideration for data analysis and interpretation.  While people are still reeling from the vast amount of data becoming available, they need to brace themselves to both discard low quality data and handle much more at the same time.  

data science: also known as data-driven science, is an interdisciplinary field of scientific methods, processes, and systems to extract knowledge or insights from data in various forms, either structured or unstructured,[1][2]similar to data mining.  … It employs techniques and theories drawn from many fields within the broad areas of mathematicsstatisticsinformation science, and computer science, in particular from the subdomains of machine learningclassificationcluster analysisdata miningdatabases, and visualization. … is now often applied to business analytics,[7] or even arbitrary use of data, or used as a sexed-up term for statistics.[8] While many university programs now offer a data science degree, there exists no consensus on a definition or curriculum contents.[7   Wikipedia accessed 2018 Jan 23

data scientist: a high-ranking professional with the training and curiosity to make discoveries in the world of big data. The title has been around for only a few years. (It was coined in 2008 by one of us, D.J. Patil, and Jeff Hammerbacher, then the respective leads of data and analytics efforts at LinkedIn and FaceBook.) … More than anything, what data scientists do is make discoveries while swimming in data. It’s their preferred method of navigating the world around them. At ease in the digital realm, they are able to bring structure to large quantities of formless data and make analysis possible. They identify rich data sources, join them with other, potentially incomplete data sources, and clean the resulting set.. … As they make discoveries, they communicate what they’ve learned and suggest its implications for new business directions. Often they are creative in displaying information visually and making the patterns they find clear and compelling. … Data scientists’ most basic, universal skill is the ability to write code. ..More enduring will be the need for data scientists to communicate in language that all their stakeholders understand—and to demonstrate the special skills involved in storytelling with data, whether verbally, visually, or—ideally—both. … Data scientists want to be in the thick of a developing situation, with real-time awareness of the evolving set of choices it presents. Data Scientist: The Sexiest Job of the 21st Century Thomas H. Davenport and D.J. Patil, Harvard Business Review Oct 2012

data stewardship: Beyond proper collection, annotation, and archival, data stewardship includes the notion of ‘long-term care’ of valuable digital assets, with the goal that they should be discovered and re-used for downstream investigations, either alone, or in combination with newly generated data. The outcomes from good data management and stewardship, therefore, are high quality digital publications that facilitate and simplify this ongoing process of discovery, evaluation, and reuse in downstream studies.: The FAIR Guiding Principles for Scientific Data Management and Stewardship  Mark D Wilkinson, Madrid, Spain; Michel Dumontier, Stanford CA, Berend Mons, Leiden Univ, Utrecht, Netherlands,

deep learning:  another hot topic buzzword – is simply machine learning which is derived from “deep” neural nets. These are built by layering many networks on top of each other, passing information down through a tangled web of algorithms to enable a more complex simulation of human learning. Due to the increasing power and falling price of computer processors, machines with enough grunt to run these networks are becoming increasingly affordable. What is Machine Learning: A complete beginner’s guide in 2017, Bernard Marr, Forbes 2017 May

deep machine learning: Deep machine learning (DML) holds the potential to revolutionize machine learning by automating rich feature extraction, which has become the primary bottleneck of human engineering in pattern recognition systems. However, the heavy computational burden renders DML systems implemented on conventional digital processors impractical for large-scale problems. The highly parallel computations required to implement large-scale deep learning systems are well suited to custom hardware. Analog computation has demonstrated power efficiency advantages of multiple orders of magnitude relative to digital systems while performing nonideal computations. In this paper, we investigate typical error sources introduced by analog computational elements and their impact on system-level performance in DeSTIN--a compositional deep learning architecture. On the impact of approximate computation in an analog DeSTIN architecture.  Young SLu JHolleman JArel I. IEEE Trans Neural Netw Learn Syst. 2014 May;25(5):934-46. doi: 10.1109/TNNLS.2013.2283730.

developability: Drug 'developability' assessment has become an increasingly important addition to traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists strive to accelerate drug discovery and development processes in a time- and cost-effective manner. D. Sun et. al, In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome. Curr Opin Drug Discov Devel.; 7(1): 75- 85, Jan 2004

diagnosis: Allen Roses, worldwide director of genetics for Glaxo Wellcome [now Glaxo SmithKline] notes that “precise diagnoses leading to universal specific treatments are, for many illnesses, myths... for many diseases there is no accurate, single diagnostic test” . A.D. Roses “Pharmacogenetics and future drug development and delivery” Lancet 355 (9212):1358-61 Apr 15, 2000   Narrower terms: companion diagnostics, molecular diagnostics

directed evolution: an iterative process scientists use to design biological molecules like enzymes. It requires inducing some randomness in the target enzyme within an organism like bacteria. The resulting mutated bacteria are screened to see which ones do the intended job the best. The winners are then cultured, and from their offspring, the best are selected, and then cultured, and so on.

a method used in protein engineering that mimics the process of natural selection to evolve proteins or nucleic acids toward a user-defined goal.[1] It consists of subjecting a gene to iterative rounds of mutagenesis (creating a library of  variants), selection (expressing the variants and isolating members with the desired function), and amplification (generating a template for the next round). It can be performed in vivo (in living cells), or in vitro (free in solution or microdroplet). Directed evolution is used both for protein engineering as an alternative to rationally designing modified proteins, as well as studies of fundamental evolutionary principles in a controlled, laboratory environment. Wikipedia accessed Sept 3 2018

directed protein evolution:  Systematic approaches to directed evolution of proteins have been documented since the 1970s. The ability to recruit new protein functions arises from the considerable substrate ambiguity of many proteins. The substrate ambiguity of a protein can be interpreted as the evolutionary potential that allows a protein to acquire new specificities through mutation or to regain function via mutations that differ from the original protein sequence. All organisms have evolutionarily exploited this substrate ambiguity. When exploited in a laboratory under controlled mutagenesis and selection, it enables a protein to "evolve" in desired directions.  Related term: phage display 

diseases: The human genome sequence will dramatically alter how we define, prevent, and treat disease. As more and more genetic variations among individuals are discovered, there will be a rush to label many of these variations as disease- associated. We need to define the term disease so that it incorporates our expanding genetic knowledge, taking into account the possible risks and adverse consequences associated with certain genetic variations, while acknowledging that a definition of disease cannot be based solely on one genetic abnormality. Disease is a fluid concept influenced by societal and cultural attitudes that change with time and in response to new scientific and medical discoveries. Historically, doctors defined a disease according to a cluster of symptoms. As their clinical descriptions became more sophisticated, they started to classify diseases into separate groups, and from this medical taxonomy came new insights into disease etiology. K Larissa et. al. "Defining Disease in the Genomics Era"  Science 293 (5531): 807- 808, Aug. 3, 2001 

Collections of symptoms and signs (phenotypes) that appear to be similar … Similar clinical phenotypes may have very different underlying mechanisms. As genetic capabilities increase, we will have additional tools to subdivide disease designations that are clinically identical. Allen D. Roses “Pharmacogenetics and future drug development and delivery” Lancet 355 (9212):1358- 1361 Apr 15, 2000

disruptive technologies: Some technologies are improved in a linear fashion or incrementally.  Others truly change the paradigm.   Clayton Christensen writes about these in The Innovator's Dilemma. What is particularly interesting about Christensen's analysis (based on data from the disk drive industry) is that he found disruptive technologies tended to be much cheaper than existing technologies. Existing companies were quite capable of developing the technologies (and had). What they couldn't do was figure out how to market them and whether it made sense to devote sufficient resources to them (which in many cases would not have been the responsible thing to do.)  

The pharmaceutical industry is mentioned only in passing, but the success of larger established companies either partnering with smaller less established ones (clearly happening in the pharmaceutical and biotechnology sectors) or spin- off of promising developments as separate companies (Johnson & Johnson said to be particularly good at this) makes a lot of sense.  
Related term: nonlinear

DNA vaccines: DNA- mediated immunization, colloquially known as DNA vaccines. This represents a radical change in the way that antigens are delivered; it involves the direct introduction of a plasmid DNA encoding an antigenic protein which is then expressed within cells of the organism. This leads to surprisingly strong immune responses, involving both the humoral and cellular arms of the immune system.  Robert G. Whelan, DNA Vaccines, Cyberspace and Self Help Programs, Intervirology 39: 120-125 (1996) DNAvaccine. com

drug: Any substance which when absorbed into a living organism may modify one or more of its functions. The term is generally accepted for a substance taken for a therapeutic purpose, but is also commonly used for abused substances. Synonymous with medicine, pharmaceutical.  [IUPAC Compendium]  

A substance recognized by an official pharmacopoeia or formulary, a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A substance (other than food) intended to affect the structure or any function of the body. A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device. Biologic products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process vs. biological process.) CDER, FDA Glossary Narrower terms: specialty pharmaceuticals. Compare biologics. 

drug development costs: Developing a drug is a risky and hugely expensive undertaking. Some 90% of publicly traded biopharmaceutical companies are not expected to make a profit this year, and, profitable or not, such companies require massive investments in research and development. How massive? The most thorough study of what it costs to a develop single new drug was conducted by three PhD economists: Joseph A. DiMasi, director of economic analysis at the Tufts Center for the Study of Drug Development, Henry G. Grabowski of Duke, and Ronald W. Hansen of the University of Rochester. Their papers on the subject go back to 1979 and have been cited by other researchers, including those of the U.S. government, to analyze policy questions. DiMasi and Grabowski wrote the chapter, “R&D Costs and Returns to New Drug Development: A Review of the Evidence,” in The Oxford Handbook of the Economics of the Biopharmaceutical Industry.  Tufts Research, Published in 2016, Examined 106 Drugs at Random  The most recent estimates of the three researchers were published in the May 2016 issue of the Journal of Health Economics. They looked at the research and development costs of 106 randomly selected drugs from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug and biologics development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval.  The researchers determined that the average out-of-pocket cost per new compound approved by the Food & Drug Administration was $1.4 billion. 

drug discovery:  For any given target, HTS High Throughput Synthesis remains the predominant tool for identifying leads for further drug development. Those companies that can effectively deal with the flood of large numbers of potential targets coming out of genomics are those that can gain a significant competitive advantage. However, this abundance of new targets is both an opportunity and a threat. When companies are able to prioritize and validate targets, it allows them to narrow the focus to those leads offering improved chances of success. Related terms: target validation

drug interactions: Examples of drug interaction terms include adverse drug interaction, drug- drug interaction, drug- laboratory interaction, drug- food interaction, etc. Drug interaction is defined as, "An action of a drug on the effectiveness or toxicity of another drug". .. Due to non- uniform usage of these terms, it is sometimes difficult to compare various studies and derive incidence rates, etc. for ADRs, and Drug Interactions   Saeed A Khan, "Drug Interaction or Adverse Drug Reaction? Confusing Terms", British Medical Journal 10 July, 1998]

Drug Safety, FDA  Related terms: idiosyncratic toxicity, pharmacovigilance

drug utilization research: was defined by WHO in 1977 as «the marketing, distribution, prescription, and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences». Since then, a number of other terms have come into use and it is important to understand the interrelationships of the different domains… Drug utilization research may also be divided into descriptive and analytical studies. The emphasis of the former has been to describe patterns of drug utilization and to identify problems deserving more detailed studies. Analytical studies try to link data on drug utilization to figures on morbidity, outcome of treatment and quality of care with the ultimate goal of assessing whether drug therapy is rational or not.  … Drug utilization research is thus an essential part of pharmacoepidemiology as it describes the extent, nature and determinants of drug exposure. Over time, the distinction between these two terms has become less sharp, and they are sometimes used interchangeably. However, while drug utilization studies often employ various sources of information that focus on drugs (e.g. aggregate data from wholesale and prescription registers) the term epidemiology implies defined populations in which drug use can be expressed in terms of incidence and prevalence … Drug utilization research also provides insight into the efficiency of drug use, i.e. whether a certain drug therapy provides value for money and the results of such research can be used to help to set priorities for the rational allocation of health care budgets. Introduction to drug utilization research, WHO World Health Organization 2003

druggable:   Able to be modulated by a small molecule to produce a desired phenotypic change in cell targets.  Variant spelling is drugable, but druggable is more common.  Alternatively/ Related terms: developability, drug-like, drug likeness, druggable, low hanging fruit, pharmaceutically tractable, privileged structure

efficacy:  Describes the relative intensity with which agonists vary in the response they produce even when they occupy the same number of receptors and with the same affinity. Efficacy is not synonymous to intrinsic activity. The property that enables drugs to produce responses. 

It is convenient to differentiate the properties of drugs into two groups, those which cause them to associate with the receptors (affinity) and those that produce stimulus (Efficacy). This term is often used to characterize the level of maximal responses induced by agonists. In fact, not all agonists of a receptor are capable of inducing identical levels of maximal responses. Maximal response depends on the efficiency of receptor coupling, i.e., from the cascade of events, which, from the binding of the drug to the receptor, leads to the observed biological effect. IUPAC Medicinal Chemistry

electroceuticals: The first logical step towards electroceuticals is to better map the neural circuits associated with disease and treatment.  This needs to happen on two levels.  On the anatomical level researchers need to map disease-associated nerves and brain areas and identify the best points for intervention. On the signalling level, the neural language at these intervention points must be decoded to develop a "dictionary" of patterns associated with health and disease states -- a project synergistic with international drives to map the human brain. 

Research teams across the globe have realised that by targeting individual nerve fibres or specific brain circuits they may soon be able to treat a wide range of conditions that have formerly relied on drug-based interventions. This could include inflammatory diseases such as rheumatoid arthritis, respiratory diseases such as asthma and diabetes. In the long run you could also control neuro-psychiatric disorders like Parkinson's and epilepsy. It wouldn't be possible to treat infectious diseases, since the bacteria and viruses that cause them aren't directly connected to the nervous system, nor would you be able to treat cancer directly in this way. However, in both cases you could stimulate the relevant nerves to boost aspects of the immune system. Electroceuticals swapping drugs for devices, Wired 28 May 2013   Related terms: bioelectronics, Genomics: optogenetics

enabling technologies: Frequently cited examples of enabling technologies for drug discovery and development are combinatorial chemistry, high-throughput screening, microarrays, bioinformatics and computational biology, nanotechnologies, and imaging (including biosensors and biomarkers).

epigenetics: For years scientists have known that biological fate is not regulated solely by DNA sequence; super ordinate regulatory mechanisms exist and contribute to determine the function of genes. Intense research has shown that these mechanisms, broadly defined as epigenetics, are multifaceted and complex. As researchers continue to decipher the roles of DNA, RNA, proteins, and environment in inheritance, the increased understanding of gene regulation and cellular differentiation from embryogenesis to aging will reveal therapeutic interventions as well as diagnostic and prognostic tools for disease.  

ethical drugs:
The old term ethical drugs signified drugs advertised only to doctors. The expression refers to the original 1847 code of ethics of the AMA, which deemed advertising directly to the public to be unethical. Over time, the term came to mean legal drugs., Independent Institute 

evidence- based toxicology: Evidence-based toxicology: a comprehensive framework for causation, Guzelian PS, Victoroff MS, Halmes NC, James RC, Guzelian CP., Hum Exp Toxicol. 2005 Apr;24(4): 161-201 

expression: The cellular production of the protein encoded by a particular gene.  The process includes transcription of DNA, processing of the resulting mRNA product and its translation into an active protein.  N.B. A recombinant gene inserted into a host cell by means of a vector is said to be expressed if the synthesis of the encoded polypeptide can be demonstrated.  IUPAC Bioinorganic, IUPAC Compendium

A description as to how a gene demonstrates a phenotype.  This can range from production of a mRNA to a disease.  If a disease gene carrier shows signs of the disease gene, then that gene is expressed.  Note that an individual must carry the disease gene and be penetrant  for it before the term expression is utilized. NHLBI  Narrower terms: gene expression, protein expression. Related terms: expression profiling, molecular profiling

expression profiling:  Expression profiling is driving the pharmaceutical R&D process. It is being used downstream of target identification, as a biological readout for target modulation. Targets first identified through genomics then need to go through validation testing, to see if a phenotypic change occurs when a target is dysregulated. These targets or pathways can be modified by using either RNAi, or the use of a chemical ligand that interacts with a target. The results are compared in order to understand a compound’s activity for on- and off- target effects. 

Refers to the expression values for a single gene across many experimental conditions, or for many genes under a single condition. In the terminology of cluster format, the first case amounts to looking at a row of the data table, and the second case a column. 

fail fast: Several high-quality analyses comparing the track record of smaller biotechnology companies with established pharmaceutical companies have concluded that company size is not an indicator of success in terms of R&D productivity … the strongest single correlator with success (odds ratio 3.9) was having a high termination rate in preclinical/Phase I stages. This indicates that companies have an early idea of which assets are likely to succeed, and that the companies most willing to face the hard decisions about which assets to terminate do better than companies that let assets linger. Does size matter in R&D productivity? If not, what does? Michael Ringel, Peter Tollman, Greg Hersch and Ulrik Schulze Nature Reviews Drug Discovery 12:901-902, Dec 2013

Designed to eliminate high risk compounds at an early stage to free up existing capacity for more successful compounds. The industry is faced with an increasing number of unvalidated or poorly validated candidates and targets. Companies risk decreasing their productivity rate if they end up chasing more low quality drug candidates. There isn't enough matter in the universe to make all possible compounds.  A term that has tended to make people in drug discovery and development wince, but considering the costs of later failures, it looks more and more like an attractive option.

FAIR data Principles : Findable, accessible, interoperable, reproducible  In the eScience ecosystem, the challenge of enabling optimal use of research data and methods is a complex one with multiple stakeholders: Researchers wanting to share their data and interpretations; Professional data publishers offering their services, software and tool-builders providing data analysis and processing services; Funding agencies (private and public) increasingly concerned with proper Data Stewardship; and a Data Science community mining, integrating and analysing the output to advance discovery. Computational analysis to discover meaningful patterns in massive, interlinked datasets is rapidly becoming a routine research activity. Providing machine-readable data as the main substrate for Knowledge Discovery and for these eScientific processes to run smoothly and sustainably is one of the Grand Challenges of eScience.

fast track: The fast track process was established in the FDA Modernization Act of 1997. Under this act, NDAs are deemed either "standard" or "priority" (fast track). With the "standard" designation, the FDA’s goal is to complete the review and make a decision on the NDA within ten months after it has been filed. With the "priority" designation, used for drugs that address unmet medical needs, the target date is six months after the filing. However, actual approval times are typically longer. In certain cases, the FDA also offers "accelerated approval" to allow the marketing of drugs for life-threatening diseases, before the benefits to patients are formally demonstrated. This approval is made on the basis of a surrogate marker (e.g., a drug’s effect on survival).

FDA US Food and Drug Administration 
DA Drug Approvals and Databases

FIPCO Fully Integrated Pharmaceutical Company:  Not as popular a goal in the 21st century as in the mid-late 1990's. 

franchises - pharmaceutical: In the pharmaceutical industry, we tend to think of franchises as a suite of relevant drugs marketed to a specific cluster of physicians. While this definition served our needs for sales efficiency and scientific credibility, it has left too much value on the table. We encourage the industry to re-think the idea of franchise in terms of brand identity, of the images, values and ideas consumers and other stakeholders, such as pharmacists, associate with a given brand. Vimal Bahuguna and Bob Lieberman, "From Patents to Franchises, Bogart Delafield Ferrier, US

function:   The vagueness of the term 'function' when applied to genes or proteins emerged as a particular problem, as this term is colloquially used to describe biochemical activities, biological goals and cellular structure. Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000

The term "function" means many things, and its meaning changes depending on who is asking the question and what sorts of experiments are being employed to probe it. Genomics by itself cannot usually determine even the biochemical, much less the cellular or physiological functions of a protein. Structural biology can determine the shape of the protein but cannot reliably determine its function; the coupling between overall structure and function is a loose one. Given a structure, one cannot determine where on the surface of a protein the likely binding sites for ligands are located and what those ligands are likely to be. Genomewide experiments have many false positives and false negatives and often do not distinguish indirect effects from direct ones. The consequences of the expression of a given gene sequence can only be determined by integrating the results from many different types of experiments, and the best way to carry out this integration is not obvious. "From Sequence to Consequence: The Problem of Determining the Functions of Gene Products in the Age of Genomics" Dr. Gregory A. Petsko, Brandeis Univ.  Chemogenomics/ Chemical Genomics Nov. 18- 19, 2002, Boston MA    Narrower terms: gene function, protein function

functional genomics:  Functional genomics aims to discover the biological function of particular genes and to uncover how sets of genes and their products work together in health and disease. In its broadest definition, functional genomics encompasses many traditional molecular genetic and other biological approaches. The development and application of global (genome- wide or system- wide) experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics [in the original more limited sense of construction of high- resolution genetic, physical and transcript maps of an organism]. It is characterized by high throughput or large- scale experimental methodologies combined with statistical and computational analysis of the results. The fundamental strategy is to expand the scope of biological investigation from studying single genes or proteins to studying all genes or proteins at once in a systematic fashion. Phil Hieter and Mark Boguski "Functional Genomics: It's All How You Read It" Science 278: 601- 602, October 24, 1997

functional proteomics:  Is yielding large databases of interacting proteins and extensive pathways maps of these interactions are being scored and deciphered by novel high throughput technologies. However, traditional methods of screening have not been very successful in identifying protein- protein interaction inhibitor

gene (cistron): Structurally, a basic unit of hereditary material; an ordered sequence of nucleotide bases that encodes one polypeptide chain (via mRNA). The gene includes, however, regions preceding and following the coding region (leader and trailer) as well as (in eukaryotes) intervening sequences (introns) between individual coding segments (exons). Functionally, the gene is defined by the cis- trans test that determines whether independent mutations of the same phenotype occur within a single gene or in several genes involved in the same function. IUPAC Compendium

There are many discussions between biologists to find a comprehensive definition of a gene, which is not easy, if possible at all. For our purposes a gene is a continuous stretch of a genomic DNA molecule, from which a complex molecular machinery can read information (encoded as a string of A, T, G, and C) and make a particular type of a protein or a few different proteins. Alvis Brazma, et. al., A quick introduction to elements of biology: 3.3 Genes and protein synthesis, European Bioinformatics Institute, Draft, 2001

Specific sequences of nucleotides along a molecule of DNA (or, in the case of some viruses, RNA) which represent the functional units of heredity. The majority of eukaryotic genes contain coding regions (codons) that are interrupted by non- coding regions (introns) and are therefore labeled split genes. MeSH, 1965

A gene is a DNA segment that contributes to phenotype/ function. In the absence of demonstrated function a gene may be characterized by sequence, transcription or homology. Human Gene Nomenclature, HUGO Genomics 79(4):464-470 (2002) 

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein NHGRI

This definition doesn't specify that it applies only to humans - but by specifying "parents" it seems to rule out non- animal genes, and almost implies mammals, or at least warm- blooded organisms.

gene disruption: A key methodology in high- throughput gene functional analysis. Involves developing various methods for systematically disrupting genes throughout the genome of a model organism (resulting in knockouts, or null mutations of these genes) and then the phenotype (if any) of the mutant organism.

gene editing: Gene editing, particularly using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, has gained importance both as a research tool in drug discovery and for drug therapy. Cambridge Healthtech Institute’s fourth annual symposium on New Frontiers in CRISPR-Based Gene Editing will bring together experts from research and clinical laboratories to talk about the recent progress in gene editing and its growing applications. However, the technology is not without limitations. What is being done to overcome some of the inherent challenges in guide RNA design, delivery and off-target effects associated with CRISPR/Cas and what are some of the alternatives being developed? Experts from pharma/biotech, academic and government labs, and technology companies will share their experiences leveraging the utility of CRISPR-based gene editing for creating cell lines and disease models, for functional in vitroin vivo and ex vivo screening, for target and cellular pathway identification, and for therapeutic use.  New Frontiers in CRISPR based Gene Editing 2018 Feb  San Francisco CA  Program  |

gene editing: Genetic engineering techniques that involve DNA REPAIR mechanisms for incorporating site-specific modifications into a cell's genome. MeSH Year introduced: 2017

gene expression: The process by which a gene’s coded information is converted into the structures present and operating in the cell.  Expressed genes include those that are transcribed into mRNA and then translated into protein and those that are transcribed into RNA but not translated into protein (e.g. transfer [tRNA] and ribosomal [rRNA] RNAs). [DOE] 

The phenotypic manifestation of a gene or genes by the processes of gene action. MeSH, 1990  Broader terms: expression, genome expression  Related term: protein expression

gene expression profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. MeSH, 2000

gene manipulation: The use of in vitro techniques to produce DNA molecules containing novel combinations of genes or altered sequences, and the insertion of these into vectors that can be used for their incorporation into host organisms or cells in which they are capable of continued propagation of the modified genes. IUPAC Biotech

gene silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. MeSH 2000 Narrower term: RNAi RNA interference

gene therapy:  Encompasses at least four types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year [1986]. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. W. French Anderson "Human gene therapy: scientific and ethical considerations" J Med Philosophy 10 (3): 275- 291, Aug. 1985  

genetic engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. MeSH, 1989  Related term: recombinant DNA technology

genetic enhancement: The use of genetic methodologies to improve functional capacities of an organism rather than to treat disease.  MeSH, 2002

The subject of much discussion and concern over the ethics of, though new disease diagnoses, treatments (and concepts of "disease") are much closer than true genetic enhancements. The popular conception of selective breeding focuses on optimization of one or a very few traits (which produces tomatoes which ship well but have no taste, and purebred dogs with congenital hip dysplasia. Little attention has been paid to the tradeoffs (predictable and not) inevitable among polygenic traits. 

"Regression to the mean" also factors in. While two tall or two bright people tend to have children who are taller or brighter than average, they are NOT usually taller or brighter than the parents are. Or as George Bernard Shaw said to the actress who told him they should have children -- "with my looks and your brain"  -- what if it turned out the other way around?  

Only microbes with their greatly enhanced opportunities for evolving (with such short reproductive spans) seem to quickly get reliably bigger, better (in a sense) and stronger. Biological homeostasis is incredibly powerful. We may never be able to "enhance" complex traits such as intelligence or strength.  But we need to learn how to talk about these issues -- preferably before actually being able to actually implement genetic enhancement.

genetic testing: Allen Roses, worldwide director of genetics for Glaxo Wellcome [now Glaxo SmithKline] notes  "Until now, government sponsored committees convened to address ‘genetic testing’ have generally limited their definition and their reports to concerns regarding diseases caused by single gene mutations … Another class of  'genetic tests’ is related to pharmacogenetics, including ... variants or other inherited polymorphic traits that are not diagnostic of disease … Clear language and differentiation of respective ethical, legal and societal issues are required to prevent inaccurate vernacular usage creating a confused public perception. Allen Roses, Pharmacogenetics and the practice of medicine” Nature 405: 857- 865, 15 June 2000   

genome: The complete set of chromosomal and extrachromosomal genes of an organism, a cell, an organelle or a virus; the complete DNA component of an organism. IUPAC Biotech

The fundamental concepts of genome, genotype and phenotype are not defined in a satisfactory manner within the biological literature. Not only are there inconsistencies in usage between various authors, but even individual authors do not use these concepts in a consistent manner within their own writings. We have found at least five different notions of genome, seven of genotype, and five of phenotype current in the literature. Our goal is to clarify this situation by (a) defining clearly and precisely the notions of genetic complement, genome, genotype, phenetic complement, and phenotype; (b) examining that of phenome; and (c) analysing the logical structure of this family of concepts. M. Mahner, M. Kary "What exactly are genomes, genotypes and phenotypes? And what about phenomes?" Journal of  Theoretical Biology 186 (1): 55- 63, May 1997

All the DNA contained in an organism or a cell, which includes both the chromosomes within the nucleus and the DNA in mitochondria. [NHGRI] Size expressed by the number of base pairs. [DOE].

First used by H. Winkler in 1920, was created by elision of the words GENes and chromosOMEs, and that is what the term signifies: the complete set of chromosomes and their genes. V McKusick "Genomics: Structural and Functional studies of genomes" Genomics 45:244-249 Oct. 15 1997

genome editing: Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism's DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome What are genome editing and CRISPR-Cas9?  Genetics Home Reference, NIH, NLM    

Genome editing
, or genome editing with engineered nucleases (GEEN) is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome of a living organism using engineered nucleases, or "molecular scissors." These nucleases create site-specific double-strand breaks (DSBs) at desired locations in the genome. The induced double-strand breaks are repaired through nonhomologous end-joining (NHEJ) or homologous recombination (HR), resulting in targeted mutations ('edits'). As of 2015 there were four families of engineered nucleases being used: meganucleaseszinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system.[1][2][3][4]  Accessed 2017 Oct 18

genomics: Generation of information about living things by systematic approaches that can be performed on an industrial scale. Roger Brent "Genomic biology" Cell 100: 169-183 Jan 2, 2000 

The systematic study of the complete DNA sequences (GENOME) of organisms. MeSH, 2001

genotype: The genetic constitution of an organism as revealed by genetic or molecular analysis, i.e. the complete set of genes, both dominant and recessive, possessed by a particular cell or organism. IUPAC Biotech

The observed alleles at a genetic locus for an individual. NHLBI

An organism’s genetic makeup, as revealed through molecular analysis.

genotyping: Used for diagnosis, drug efficacy, and toxicity. Utilizes genomic DNA that, after digestion, reacts with a SNP array to obtain an individual SNP pattern. These variations can for instance provide information about the diagnosis of a certain disease, or the effectiveness or side effect of a certain drug.  May refer to identifying one or more, up to the entire gene sequence of an organism. Compare phenotype Genotyping implies (though I haven't found this in print) determining known variants, as opposed to discovery of new ones.

granularity: Level of detail.  As we learn more and more about biology we find that older concepts are not so much wrong, but that what we knows becomes more and more granular, and we learn more about what we don't yet know or understand. 

GWAS Genome Wide Association Sequencing: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition. MeSH 2009

The NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of basic biological processes affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine.   Pronounced "gee-wahs"

haplotypes:  The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. MeSH 1987

haplotyping: Somatic cells, as opposed to germ cells, have two copies of each chromosome. A given single- base position may be homozygous for the wild- type base (each chromosome has the normal allele), homozygous for a SNP base (each chromosome has the altered allele), or heterozygous for two different bases (one chromosome has the normal allele and the other has the abnormal allele).  Haplotyping involves grouping subjects by haplotypes, or particular patterns of sequential SNPs, found on a single chromosome. These SNPs tend to be inherited together over time and can serve as disease- gene markers. The examination of single chromosome sets (haploid sets), as opposed to the usual chromosome pairings (diploid sets), is important because mutations in one copy of a chromosome pair can be masked by normal sequences present on the other copy.  Genes tend to travel in packs. This is good news for pharmacogenomics.  Broader terms genotyping, sequencing

high-content screening HTS: By using multiple fluorescent reporter systems, combined with high- resolution imaging and high- throughput image analysis, researchers can observe multiple intracellular events in individual cells. High- content screening (HCS) enables functional analysis of target and pathway modulation in living cells by potential drug compounds. Availability of high- content cellular information at early stages in drug discovery process will improve the quality of targets, hits, and leads; reduce late- stage attrition; and shorten time and cost of drug development.

high tech industry: The traditional perception of high tech - still reflected in our indicators - has been research- intensive manufacturing industries, like computers and aircraft. The penetration of technologies like information technology, biotechnology, and advanced materials throughout the economy has, however, changed the basic meaning of high tech. Rather than referring to the output of R&D intensive industries, high tech now refers to a style of work applicable to just about every business ... This change is said to have revolutionized the features of a successful technology policy. Distributed knowledge, skill, entrepreneurship, together with new forms of collaboration between firms, universities and the government, can now result in more effective products and services.  Importantly for both firm and worker income, they can result in significantly differentiated products and services. In other words, technology policy must be more user- centered and demand- based than ever before. Nicholas S. Vonortas "US Policy towards Research Joint Ventures" Nov. 1999 

high throughput: Although the adjective "high throughput" was originally coined in a drug screening context, high throughput strategies to accelerate and automate earlier steps in the drug discovery pipeline have already been introduced. With the introduction of genomics- based drug discovery strategies, the concept of high throughput has extended to areas like gene expression analysis, where microarrays allow the simultaneous expression profiling of thousands of genes in diseased versus normal samples. In the early stages of disease- gene research, when one wishes to identify alterations in gene expression that are associated with a disease state with significant societal impact and potential market value, a microarray- based approach provides significant acceleration over traditional methods to evaluate candidate genes one at a time.  

high throughput screening:  Process for rapid assessment of the activity of samples from a combinatorial library or other compound collection, often by running parallel assays in plates of 96 or more wells. IUPAC Combinatorial Chemistry

Traditionally describes the running of a large-scale assay campaign looking at the effects of a large number of compounds on a biological target. 
Broader term: screening  Narrower terms: high content screening, ultra high throughput screening  Related term: high throughput

Human Genome Project HGP: Horace Freeland Judson writes in "Talking about the genome" (Nature 409:769, 15 Feb. 2001) "The language we use about genetics and the genome project at times limits and distorts our own understanding, and the public understanding. Look at the phrase - or marketing slogan - 'the human-genome project'. In reality, of course we have not just one human genome but billions. ... Then, too, the entire phrase - the human- genome project: singular, definite, with a fixed end- point, completed by 2000, packaged so it could be sold to legislative bodies, to the people, to venture capitalists. But we knew from the start the genome project would never be complete. 

human induced pluripotent stem cells hiPS: Reprogramming differentiated human cells to induced pluripotent stem (iPS) cells has applications in basic biology, drug development, and transplantation. Human iPS cell derivation previously required vectors that integrate into the genome, which can create mutations and limit the utility of the cells in both research and clinical applications. Here, we describe the derivation of human iPS cells using non-integrating episomal vectors. After removal of the episome, iPS cells completely free of vector and transgene sequences are derived that are similar to human embryonic stem (ES) cells in proliferative and developmental potential. Junying Yu 1*, Kejin Hu 2, Kim Smuga-Otto 1, Shulan Tian 3, Ron Stewart 3, Igor I. Slukvin 4, James A. Thomson 5* Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences, Science DOI: 10.1126/science.1172482 published online March 26, 2009

hypercompetitive:  In Richard A. D'Aveni's Hypercompetitive Rivalries: Competing in Highly Dynamic Environments, (1995) he describes situations in which competitive advantages are not sustainable. Companies must be willing to cannibalize their own customers and positions, making all products obsolete including their own. The pharmaceutical industry is sometimes described as hypercompetitive.

hyphenated techniques: Usually involves a combination of chromatography and/ or mass spectrometry, NMR or other spectroscopy  technologies.

idiosyncratic toxicity: Few drug development surprises can be as devastating as toxicity problems that only show up under a combination of conditions as idiosyncratic toxicity. Because of the role of variations in human drug metabolizing enzymes there may only be subtle (or no) evidence of such problems during pre-clinical safety studies. Such problems are also unlikely to show up in all but the largest clinical trials, but if the side effects are serious, it can result in product withdrawal. 

ill posed problems:  In the 1960s [Russian mathematician Andrei Nikolaevich] Tikhonov began to produce an important series of papers on ill- posed problems. He defined a class of regularisable ill- posed problems and introduced the concept of a regularising operator which was used in the solution of these problems. Combining his computing skills with solving problems of this type Tikhonov gave computer implementations of algorithms to compute the operators which he used in the solution of these problems.. "Andrei Nikolaevich Tikhonov", MacTutor History of Mathematics, Univ. of St. Andrews, Scotland, 1999 

Problems without a unique solution, problems without any solution.  Life sciences data tends to be very noisy, leading to ill-posed problems. Interpretation of microarray and gene expression data is an ill- posed problem. Compare well- posed problem

immunotherapy: A type of biological therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies. NCI Dictionary of Cancer terms 

in silico: In a white paper I wrote for the European Commission in 1988 I advocated the funding of genome programs, and in particular the use of computers. In this endeavour I coined "in silico" following "in vitro" and "in vivo" I think that the first public use of the word is in the following paper: A. Danchin, C. Médigue, O. Gascuel, H. Soldano, A. Hénaut, From data banks to data bases. Res. Microbiol. (1991) 142: 913- 916.  You can find a developed account of this story in my book The Delphic Boat, Harvard University Press, 2003 personal communication Antoine Danchin, Institute Pasteur, 2003

Literally "in the computer".   Narrower terms: in silico biology, in silico modeling, in silico proteomics, in silico screening, in silico target discovery, virtual cells in silico  Compare in vivo, in vitro

in vitro diagnostics: The process of developing a successful in vitro diagnostic (IVD) relies on the expertise of a diverse group of individuals, including the scientists who identify the biomarkers of significance, engineers and assay developers who translate those ideas into a tangible product, and the sales and marketing staff who get the product into the market. Global and regional trends have a tremendous effect on the IVD industry. Rising healthcare costs have led to a greater emphasis on evidence-based medicine and a focus on improved patient outcomes. An aging population along with the growing epidemic of chronic diseases and (re)emergence of infectious diseases are creating a demand for diagnostic devices for a variety of conditions. The growth of emerging economies and the push for decentralized healthcare are opening the IVD market to a wider audience. Healthcare delivery systems are changing, with growing numbers of integrated delivery networks and accountable care organizations, while smaller physician and hospital networks are being acquired by larger corporations and/or are aligning themselves with other small groups. Commercializing Novel IVDs , Harry Glorikian, Insight Pharma Reports\   Executive Summary 

informatics: The study of the application of computer and statistical techniques to the management of information. In genome projects, informatics includes the development of methods to search databases quickly, to analyse DNA sequence information, and to predict protein sequence and structure from DNA sequence data. [ORD Office of Rare Diseases, NIH glossary] 
Narrower terms: bioinformatics; cheminformatics; clinical informatics, molecular informatics, pharmacoinformatics, protein informatics, research informatics  

information overload: 

information silos: The cultural aspects impeding communication between different groups can be immense, are often not recognized or articulated, and greatly impede interdisciplinary research. 

interdisciplinary: Terminology and ideas relevant to molecular medicine comes from a wide variety of disciplines: analytical chemistry, artificial intelligence, biochemistry, bioinformatics,  biomechanics, biophysics, biotechnology, cell biology, clinical and research medicine, computer sciences, developmental and structural biology, electrochemistry, electronics, engineering, enzymology, epidemiology, genetic engineering, molecular imaging, immunology, mathematics, microbiology, molecular biology, optics, pharmacology, public health, statistics, toxicology, virology and aspects of business, chaos theory, ethics and law are all relevant. Few people (if any) can be truly interdisciplinary and expert in all of these subjects. Universities and companies are struggling with the challenge of (and need to) build bridges between departments and sectors.  We all need to learn more to participate in informed public debate

interoperability:  Ability of a system or a product to work with other systems or products without special effort on the part of the customer. Interoperability is made possible by the implementation of standards. IEEE, Standards Glossary 2010

Enabling heterogeneous databases to function in an integrated way, sometimes refers to cross platform functionality and operability across relational, object- oriented, and non- standard types of databases.  Related term: FAIR Data

"junk DNA": A general term that encompasses many different types of DNA sequences. These sequences run the gamut from introns, the parts of genes that are edited out during protein synthesis; transposable elements, repeated DNA sequences that, like parasites, duplicate themselves, adding nothing to the genome except more redundant sequence; and pseudo genes, fossils of one- time genes…all of the regulatory elements – promoters and inhibitors - required for gene transcription are spelled out somewhere between the genes. The same is true of other elements deemed junk, such as introns and RNA genes, which clearly hold important clues to understanding alternative splicing … the term junk DNA is frequently used incorrectly. Numerous articles in the medical literature use junk and non- coding DNA interchangeably. B. Kuska "Bring in Da Noise, Bring in Da Junk" JNCI 90(15): 1125-1127 Aug. 5, 1998

Dr. Susumu Ohno, writing in the Brookhaven Symposium on Biology in 1972 in the article "So Much ‘Junk DNA" in our Genome’ is credited with originating the term. But his paper was focused "mainly on the fossilized genes, called pseudo genes, that are strewn like tombstones throughout our DNA. But as the term caught on in the 1980’s, its meaning was extended to all non- coding sequences, the vast stretches of DNA that are not genes and do not produce proteins" (about 95% of the genome) … some [scientists] have begun the scrap the notion that all non- coding DNA is junk …  "I don't think people take the term very seriously anymore" says Eric Green [NHGRI] whose group is mapping chromosome 7. B. Kuska "Should Scientists Scrap the Notion of Junk DNA?" JNCI 90(14): 1032-1033 July 15 1998  Narrower terms  intron, non- coding, repetitive sequences.

knockdowns: Altering the function of a gene so that it can be conditionally expressed. This is necessary when complete knockout of the gene would be lethal to the organism. |
Related terms: antisense, embryonic lethal trait, knockin, knockout, RNAI RNA Interference  Narrower term: genomewide knockdowns

knockins: Gain of function through addition/ substitution of genetic material. One example of a knockin is deletion of a coding sequence of a gene in a mouse and then replacing it with human coding sequences.

knockouts: Inactivation of specific genes. Knockouts are often created in laboratory organisms such as yeast or mice so that scientists can study the knockout organism as a model for a particular disease. [NHGRI] 

Use of particular techniques to "knock out" the function of a gene in a model organism. Studying the effects of the gene knockout can help researchers understand the function of the gene that has been inhibited.  Narrower terms: conditional knockout, random homozygous knockout Related terms gene knockout, knockdown, knockin, protein knockouts

Laboratory Developed Tests LDTs: A laboratory developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used within a single laboratory. ... For example, sometests can detect many DNA variations from a single blood sample, which can be used to help diagnose a genetic disease.  FDA, LDTs

The Coverage and Analysis Group at the Centers for Medicare & Medicaid Services (CMS) requested from The Technology Assessment Program (TAP) at the Agency for Healthcare Research and Quality (AHRQ) a horizon scan to summarize the available scientific evidence on the quality of laboratory-developed ("home brew" or "in-house") molecular tests, which are currently not actively regulated by the U.S. Food and Drug Administration (FDA). CMS has concerns about the quality of laboratory-developed tests and the validation currently being performed on these tests . AHRQ assigned this report to the following Evidence-based Practice Center (EPC): ECRI EPC (Contract Number: 290 2007 10063 I). To help CMS to address its concerns, this horizon scan is intended to: 1) identify types of laboratory-developed molecular tests (LDMTs) currently available for conditions relevant to the Medicare over-65-year-old population, 2) identify the methodologies and the processes that have been developed for the assessment of analytical and clinical performance of molecular tests, 3) summarize the role of Federal agencies in regulating LDMTs, and 4) identify the quality standards that have been developed for molecular tests by regulatory bodies, the industry, and the medical community.   See also Analyte Specific Reagents

lead optimization: The synthetic modification of a biologically active compound, to fulfill all stereoelectronic, physicochemical, pharmacokinetic and toxicologic required for clinical usefulness. IUPAC Medicinal Chemistry

Fueled by the need to bring down the cost of drug discovery and development, a major shift is occurring in how pharmaceutical companies evaluate drug leads. Whereas researchers used to begin by looking at affinity and potency, a genomics/informatics- based research culture is growing and starting to impinge on the classical mode. Companies are now concentrating on determining potential drugs leads' ADMET (absorption, distribution, metabolism, excretion, and toxicological) properties and manufacturability.
Related terms: ADME, ADMETox, drug development. Narrower terms:  lead discovery, lead prioritization, lead selection, lead validation, toxicogenomics, parallel optimization

library: An unordered collection of clones (i.e., cloned DNA from a particular organism), whose relationship to each other can be established by physical mapping. [DOE] 
Narrower terms: cDNA libraries, chemical libraries, combinatorial library, compound libraries, DNA library, gene library, genomic library, hit optimization library, lead discovery library,  biased libraries, combinatorial antibody libraries, directed libraries, focused libraries, pool, pool/ split libraries, sub- library, random libraries, unbiased libraries; 

life cycle management:  Successful drugs follow a typical pattern of heavy up- front investment in development, followed by market penetration and peaking sales, followed by a decline in the face of follow- on drugs or generics. A number of approaches can be used to alter the shape of this revenue curve, including second- generation follow- on compounds, extended life through formulation and drug delivery enhancements, outcome studies and management of the generification process. Some steps can be taken early to maximize the benefits of drug life cycle management. 

life sciences informatics: Informatics are essential at every step of genomics-based drug discovery and development. The commercial landscape of life sciences information technology has changed dramatically in the last few years. Bioinformatics, in particular, has gone through a dramatic boom/bust. While IT companies are looking to the drug discovery and development arena as a new market opportunity, pharmaceutical companies  are faced with rising pressure to reduce (or at least control) costs, and have a growing need for new informatics tools to help manage the influx of data from genomics, and turn that data into tomorrow's drugs. Key IT tools, such as high- performance computing, Web services, and grids, are being used to improve the speed and efficiency of drug discovery and development. True breakthroughs are still lacking, particularly in key areas such as gene prediction, data mining, protein structure modeling and prediction, and modeling of complex biological systems. However, most experts agree that IT and bioinformatics are essential to reaching the improved productivity the pharmaceutical industry craves.  

life style drugs: Drugs treating conditions such as  obesity, erectile dysfunction, baldness, aging.  The attraction is a steady market for which consumers may well be willing to pay for.

low hanging fruit: The easiest drugs to identify and gain approval for.  The big question these days is how much (if any) "low hanging fruit" is left. 

machine learning: At its most simple, machine learning is about teaching computers to learn in the same way we do, by interpreting data from the world around us, classifying it and learning from its successes and failures. In fact, machine learning is a subset, or better, the leading edge of artificial intelligence. How did machine learning come about?  Building algorithms capable of doing this, using the binary “yes” and “no” logic of computers, is the foundation of machine learning – a phrase which was probably first used during serious research by Arthur Samuel at IBM during the 1950s. Samuel’s earliest experiments involved teaching machines to learn to play checkers.  … For example, in medicine, machine learning is being applied to genomic data to help doctors understand, and predict, how cancer spreads, meaning more effective treatments can be developed.  What is Machine Learning: A complete beginner’s guide in 2017, Bernard Marr, Forbes 2017 May

A type of ARTIFICIAL INTELLIGENCE that enable COMPUTERS to independently initiate and execute LEARNING when exposed to new data.  Year introduced: MeSH  2016

market forecasting- pharmaceutical:   Accurately forecasting the market potential for new compounds is becoming an essential tool in long- term strategic planning, as it aids in various decisions that are pivotal to the survival and success of a biotech or pharmaceutical company. Forecasting is used in many situations: to evaluate a licensing opportunity, to assess a particular lead compound and even in pipeline and R&D portfolio analyses. Forecasting is also essential in understanding how the dynamics of a market are changing, and in raising awareness of a company's current and future competitors. .. Top- down forecasting extrapolates from available sales data, using algorithms of how a particular drug class or market has previously performed. Bottom- up forecasting involves reconstructing the market from its components, which allows the analyst to model how particular changes over the forecast period will affect the base- year assumptions.  John Earl "What makes a good forecaster?" Nature Reviews Drug Discovery 2(1): 83, Jan. 2003

market fragmentation - pharmaceutical industry:  Currently, the percentage of patients that react favorably to a drug ranges from 20-80%. The market segments itself as patients and doctors switch between medications in order to find the one that works. In fact, market share may erode further, even in the absence of significant competition, as physicians avoid prescribing a drug if a subset of patients suffer toxic side effects. By defining the population that responds well to a drug, pharmacogenomics can help secure market share. Blockbusters are still possible if the defined population is large. 

mass spectrometry: This technique can be used to both measure and analyze molecules under study. It involves introducing enough energy into a target molecule to cause its ionization and disintegration. The resulting fragments are then analyzed, based on the mass/ charge ratio to produce a "molecular fingerprint."  

A significant technology behind progress in proteomics

medical informatics:  The field of information science concerned with the analysis and dissemination of medical data through the application of computers to various aspects of health care and medicine. MeSH, 1987

medicinal chemistry: A chemistry based discipline, also involving aspects of biological, medical and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure- activity relationships  IUPAC Medicinal Chemistry

megabrands: drugs that post sales of $1 billion in more than 50 countries within two years of their launch. IMS Reviews Pharma Growth and Outlines Future Trends  ICS Chemical Business 2000

Mendelian genetics: Classical genetics, focuses on monogenic genes with high penetrance, the tip of the iceberg of genetics.  Genomics is both a narrower and broader term than genetics

Metabolic Engineering ME: An approach to the understanding and utilization of metabolic processes. As the name implies, ME is the targeted and purposeful alteration of metabolic pathways found in an organism in order to better understand and utilize cellular pathways for chemical transformation, energy transduction, and supramolecular assembly. ME typically involves the redirection of cellular activities by the rearrangement of the enzymatic, transport, and regulatory functions of the cell through the use of recombinant DNA and other techniques. Much of this effort has focused on microbial organisms, but important work is being done in cell cultures derived from plants, insects, and animals. National Science Foundation, Interagency Opportunities in Metabolic Engineering,  Program Solicitation NSF 05-502, 2004 

metabolic profiling:  For investigators of selected biochemical pathways, it is also often not necessary to view the effects of perturbation on all branches of metabolism. Instead, the analytical procedure can be focused on a smaller number of pre- defined metabolites. Sample preparation and data acquisition can be focused on the chemical properties of these compounds with the chance to reduce matrix effects. This process is called metabolite profiling (or sometimes metabolic profiling). Oliver Fiehn "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2: 155-168, 2001

metabolism: In case of heterotrophic organisms, the energy evolving from catabolic processes is made available for use by the organism.   IUPAC Medicinal Chemistry

The sum of chemical changes that occur within the tissues of an organism consisting of anabolism (BIOSYNTHESIS) and catabolism; the buildup and breakdown of molecules for utilization by the body. MeSH

The total fate of a xenobiotic, which includes: absorption, distribution, biotransformation, metabolism and elimination (ADME). Metabolism and biotransformation are often used interchangeably, but the latter term does not encompass absorption, distribution and elimination.  Glossary, XenoTech LLC  

Metabolism, Wikipedia, accessed May 27, 2004 distinguishes between total metabolism, specific metabolism, cell metabolism and other types of metabolism.

metabolite: Any intermediate or product resulting from metabolism. IUPAC  International Union of Pure and Applied Chemistry, Glossary for Chemists of terms used in biotechnology. Recommendations, Pure & Applied Chemistry 64 (1): 143-168, 1992

metabolomics:  The study of the metabolite profiles in biological samples, is growing amidst the current shift toward translational research. Although there is some debate over what the field should actually be called, scientists are pushing forward to find uses for metabolomic profiling, a clinical option that is comparatively cheap and noninvasive. Charles W. Schmidt, Metabolomics: What's happening downstream of DNA, EHP online Environmental Health Perspectives, Toxicogenomics, 2004 

The general aim of metabolomics is to identify, measure and interpret the complex time-related concentration, activity and flux of endogenous metabolites in cells, tissues, and other biosamples such as blood, urine, and saliva.  For the purposes of this solicitation, metabolites include small molecules that are the products and intermediates of metabolism, but also carbohydrates, peptides, and lipids… It is expected that the technologies developed under this initiative will play a major role in transferring capabilities to laboratories and research institutes that are investigating the underlying pathways involved in cellular homeostasis, perturbation, development, and aging. NIH Guide Metabolomics Technology 2004 

Due to pleiotropic effects, the effect of a single mutation may lead to the alteration of metabolite levels of seemingly unrelated biochemical pathways.  This is especially liable to happen if genes are constitutively overexpressed or anti- sense inhibited. A comprehensive and quantitative analysis of all metabolites could help researchers understand such systems.  Since such an analysis reveals the metabolome of the biological system under study, this approach should be called metabolomics.  Analogous to proteins and proteomics, metabolomics, or metabonomics, is the study of all the metabolites of a cell or organism. Identifying and quantifying these components helps to reveal cellular regulation, pathways, activity, and response under normal and other conditions. Brush up on your 'omics, Chemical & Engineering News, 81(49): 20, Dec. 2003 

For functional genomic or plant breeding programmes, as well as for diagnostic usage in industrial or clinical routines, it might not be necessary to determine the levels of all metabolites individually. Instead, a rapid classification of samples according to their origin or their biological relevance might be more adequate in order to maintain a high through- put. This process can be called metabolic finger- printing. Such approaches have occasionally been termed metabonomics, which on the one hand could be mixed up with the completely different goal of metabolomics, and on the other hand with the earlier defined concept of the metabolon, the coordinated channelling of substrates through tightly connected enzyme complexes.  Oliver Fiehn, "Combining genomics, metabolome analysis and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2:155-168 April, 2001

metabonome, metabonomics: The quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. This concept has arisen from work on the application of  1H-NMR spectroscopy to study the multicomponent measurement of biofluids, cells, and tissues. [J.K. Nicholson, J.C. Lindon & E. Holmes, "Metabonomics" understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29, 1181-1189, 1999] 

Total small molecule complement of a cell. [Jeremy K. Nicholson, J.C. Lindon & E. Holmes. "Metabonomics": understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29, 1181-1189, 1999]  

microarrays: Tool for studying how large numbers of genes interact with each other and how a cell’s regulatory networks control vast batteries of genes simultaneously. Uses a robot to precisely apply tiny droplets containing functional DNA to glass slides. Researchers then attach fluorescent labels to DNA from the cell they are studying. The labeled probes are allowed to bind to cDNA strands on the slides. The slides are put into a scanning microscope to measure … how much of a specific DNA fragment is present. [NHGRI]  

Roger Brent has compared microarrays to the telescope or microscope because they enable the observer to see what was previously unobservable.
Alternatively: arrays, gene chips, SNP chips  Related terms: antibody arrays,  protein chips

microdosing: Almost half of new drugs fail at the transition from animal to human trials. Human microdosing points the way to smarter drug development and may be the answer to what has been perceived as a productivity crisis in the industry.  By testing only 1% of a pharmacological dose in humans, failures can be identified much earlier in the development process – at Phase 0. This approach has proven to be successful in ADME prediction, helping scientists identify which candidates merit further development.  Microdosing technology can also be used to determine absolute bioavailability, thus aiding drug developers to assess pharmacodynamics and physiological activity. Gathering scientists together to discuss this new and important tool certainly seems needed in order to promote faster, more efficacious drug development.  Using microdosing shows promise of reducing time spent on drugs destined to fail, and also cutting down on the costs associated with testing. In addition, human microdosing at Phase 0 will mitigate the need for testing in animals, and can also help to determine the best animal models to use. Microdosing studies have become possible due in large part to the technical advances of detection instruments.

miniaturization: Desirable for many technologies for overall cost reduction (including reduction in the amount of reagents and analytes needed). Important to remember that building space is often the least available and most expensive component of a laboratory budget.

molecular diagnostics techniques: MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENTIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with PCR (POLYMERASE CHAIN REACTION).  MeSH, 2002

molecular epidemiology: The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples. MeSH, 1994

Looking at epidemiology from a genetic/genomic and/or biochemical viewpoint.

molecular medicine:  The Journal of Molecular Medicine publishes reports describing major advances in the understanding, prevention, diagnosis, or treatment of human disease through the application of molecular biology and gene technology, a research discipline that has become known as molecular medicine.. Journal of Molecular Medicine, Springer, Aims and Scope Alternatively/related terms: clinical genomics, predictive medicine

molecular modeling, molecular modelling: A technique for the investigation of molecular structures and  properties using computational chemistry and graphical visualization techniques in order to provide a plausible three- dimensional representation under a given set of  circumstances. IUPAC Medicinal Chemistry, IUPAC Computational  
Related terms: CADD Computer Assisted Drug Design, in silico, molecular graphics, molecular dynamics, virtual screening

molecular pathology: What is new in "molecular pathology" is the emphasis on assessing gene expression in addition to morphology, and the use of gene expression analysis to validate large numbers of targets. (However, histochemistry and immunohistochemistry have been used, for specific proteins, since before the advent of genomics.) Corporate genomic researchers are increasingly seeking access to human tissue samples via collaborations with pathology departments at clinical research institutions.

monoclonal antibodies: A single species of immunoglobulin molecules produced by culturing a single clone of a hybridoma cell. MAbs recognize only one chemical structure, i.e., they are directed against a single epitope of the antigenic substance used to raise the antibody. IUPAC Biotech

Antibodies produced by clones of cells such as those isolated after hybridization of activated B lymphocytes with neoplastic cells. These hybrids are often referred to as hybridomas. MeSH, 1982
Broader term: antibody  Related terms: cloning,
hybridoma, fully humanized antibodies, therapeutic antibodies, polyclonal antibodies

multibusters: Multiple drugs for a single indication, efficacious in identifiable sub- populations.  Related term: blockbuster drugs

multiplex:  A sequencing approach that uses several pooled samples, greatly increasing sequencing speed. DOE

Simultaneous amplification of multiple gene products within the same reaction. Chamberlain, J.S. et al. Nucleic Acids Research 16, 11141, 1988

In general, primer- extension technologies are amenable to high- throughput applications and automation, yet only very low levels of multiplexing are possible. Higher multiplexing can be accomplished by combining primer- extension technology with microarray technology. 

Originally a math term meaning multiple, later a 19th century telecommunications term, dating from the telegraph. Oxford English Dictionary

nanomedicine:  The monitoring, repair, construction and control of human biological systems at the molecular level, using engineered nanodevices and nanostructures. [Robert A. Freitas, Nanomedicine, Foresight Institute, 1998- 2002]

Obtaining thorough, reliable measures of quantity is the vital first step of nanomedicine. … Research conducted over the first few years will be spent gathering extensive information about how molecular machines are built. A key activity during this time will be the development of a new kind of vocabulary —lexicon — to define biological parts and processes in engineering terms. …Once researchers have completely catalogued the interactions between and within molecules, they can begin to look for patterns and a higher order of connectedness than is possible to identify with current experimental methods. Mapping these networks and understanding how they change over time will be a crucial step toward helping scientists understand nature’s rules of biological design. Understanding these rules will, in many years’ time, enable researchers to use this information to address biological issues in unhealthy cells. The availability of innovative, body-friendly nanotools will help scientists figure out how to build synthetic biological devices, such as miniature, implantable pumps for drug delivery or tiny sensors to scan for the presence of infectious agents or metabolic imbalances that could spell trouble for the body. NHGRI, Nanomedicine, 2007 

The goal of the Common Fund's Nanomedicine program is to determine how cellular machines operate at the nanoscale level and then use these design principles to develop and engineer new technologies and devices for repairing tissue or preventing and curing disease. Nanomedicine, NIH Common  Fund

Nanomedicine Taxonomy

nanoscience:  The study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale. Draft definitions, Royal Society, Royal Academy of Engineering  Nanotechnology and Nanoscience, 2003 
Narrower terms: nanobiology, nanobiotechnology, nanochemistry, nanoengineering, nanophysics.
Alternatively nanotechnology Related terms: quantum physics

NCE New Chemical Entity A compound not previously described in the literature. IUPAC Medicinal Chemistry   Compare: me too drug  

NDA New Drug Application: For decades, the regulation and control of new drugs in the United States has been based on the New Drug Application (NDA). Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization.  The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. 

networks: Although there is no consensus definition of "program" or "networks", these terms are most often encountered and understood in the context of the regulatory interactions that link groups of genes and gene products in developmental processes.  Many of these linkages have recently been elucidated in considerable detail for key events in a variety of species. Sean Carroll "Communications breakdown?" (book review) Science 291: 1264-1265, Feb. 16, 2001

There are three bottlenecks in the numerical analysis of biochemical reaction networks. The first is the multiple time scales involved. Since the time between biochemical reactions decreases exponentially with the total probability of a reaction per unit time, the number of computational steps to simulate a unit of biological time increases roughly exponentially as reactions are added to the system or rate constants are increased. The second bottleneck derives from the necessity to collect sufficient statistics from many runs of the Monte- Carlo simulation to predict the phenomenon of interest. The third bottleneck is a practical one of model building and testing: hypothesis exploration, sensitivity analyses, and back calculations, will also be computationally intensive. [Lawrence Berkeley Lab "Advanced Computational Structural Genomics" Glossary]  Narrower terms: biochemical networks, molecular networks.  Related terms: network models, pathways

new paradigms:  An investigation by Science revealed that use of the term "new paradigm" in MEDLINE and the ISI database of leading journals increased steadily during the 1990’s, as did its use in NIH and NSF databases of new grants. J Cohen "The March of Paradigms" Science 283 : 1998-1999 Mar 26, 1999 

While many advances are unlikely to be truly new paradigms, a few developments show signs of being more than incremental improvements. Roger Brent compares microarrays to the microscope and telescope because they "enable observation of the previous unobservable" [transcripts expressed under different conditions in cells, tissues, and organisms] [R. Brent, "Functional genomics: learning to think about gene expression data" Current Biology 9: R338-R341, May 1999] This is no overstatement.

next generation sequencing: Next-generation sequencing (NGS) has taken the worldwide biomedical research community by storm. Funding is relatively abundant for the moment, collaborative programs and consortia abound, and early results in many cases appear to justify all the activity. Many observers sense imminent new revelations and even paradigm shifts offering significant improvements in the understanding and treatment of disease. Insight Pharma Reports  Next-Generation Sequencing Technologies: Applications and Markets 2010  

NME New Molecular Entity:  A New Molecular Entity is an active ingredient that has never before been marketed in the United States in any form. FDA, Glossary Drugs@FDA,  2012, 

NMR Nuclear Magnetic Resonance: A technology for protein structure determination. NMR generally gives a lower- resolution structure than X-ray crystallography does, but it does not require crystallization. .

nonlinear: Advances in biopharmaceutical  technologies are a mix of incremental improvements to existing technologies (linear) and occasionally, a truly new paradigm or breakthrough.   
Related terms:
disruptive technologies, emerging technologies, biocomplexity, complex

nutraceuticals: Foods with specific health or medical benefits. Differentiate from supplements, which supplies missing nutrients. Examples include folic acid (to prevent birth defects) or pectin (to lower cholesterol) and fiber (to reduce the risk of color cancer). Sometimes spelled nutriceutical.

off label: The use of an FDA- approved drug or device for a purpose other than that intended by the manufacturer and described on the label. FDA only approves drugs or devices for their intended use as described on the label. Neal Holtzman, Michael Watson "Promoting Safe and Effective Genetic Testing in the United States: Final Report" glossary, 1997

-omes: A key approach in genomic research is to divide the cellular contents into distinct sub- population, each given an -omic term. Broadly, these 'omes can be divided into those that represent a population of molecules, and those that define their actions. ... Once the individual sub- populations are defined and analyzed, we can then try to reconstruct the full organism by interrelating them, eventually allowing for a full and dynamic view of the cell. ... A problem in comparing the different 'omes' is that each represents a different set of genes. Mark Gerstein "What is Bioinformatics?" Molecular Biology & Biochemistry 474b3, Yale Univ. 2001

In physics, probably starting with Faraday's ion, cation, anion, the -on suffix has tended to signify an elementary particle, later materially focused on the photon, electron, proton, meson, etc., whereas -ome in biology has the opposite intellectual function, of directing attention to a holistic abstraction, an eventual goal, of which only a few parts may be initially at hand.  Joshua Lederberg and Alexa T. McCray "'Ome Sweet 'Omics: A Genealogical Treasury of Words" Scientist 15 (7): 8 April 2, 2001  

According to the Oxford English Dictionary this is an Anglicized version of the suffix "oma", primarily found in botanical terms and usually  meaning normal, in contrast to the pathology implied by "oma".

ontologies: What is an ontology?, W3C, Requirements for a web ontology language, [work in progress]

optogenetics: A rapidly evolving field of technology that allows optical control of genetically targeted biological systems at high temporal and spatial resolution. By heterologous expression of light-sensitive microbial membrane proteins, opsins, cell type-specific depolarization or silencing can be optically induced on a millisecond time scale. … Although recent developments in optogenetics have largely focused on neuroscience it has lately been extended to other targets, including stem cell research and regenerative medicine. The optogenetic (r)evolution, Martin L Rein, Jan M. Deussing, Mol Genet Genomics. 2012 February; 287(2): 95–109, Published online 2011 December 20. doi: 

organization of pharmaceutical R&D: By far the most common organizational structure within pharmaceutical R&D is based on therapeutic indications. As target pathways and target families become better recognized as opportunities for synergistic development that cut across disease indications, what are the implications for how best to capture this synergy? As molecular tools are increasingly applied beyond target biology to more of the entire development process, how can expertise in specific tools best be leveraged across different departments? As chemistry and biology become more intertwined, how can researchers trained in one discipline or the other learn to better communicate with each other? As researchers trained in reductionist techniques and used to working on small projects become involved in much larger systems biology and high throughput chemistry projects, how does this change the nature of the work they do? What organizational structures and policies may facilitate optimal performance under these changing conditions? 

I have hoped drug companies which encouraged open sharing of scientific information would prosper in the long run, without finding much evidence (even anecdotal) until I read this report, which quantified the positive correlation between companies encouraging peer reviewed scientific publication and productivity (patents issued to company scientists and articles published in peer- reviewed journals by company scientists). Diffusion of Science Driven Drug Discovery Organizational Change in Pharmaceutical Research,  Iain M. Cockburn, Rebecca Henderson and Scott Stern, NBER, Sept. 1999  

orphan drugs: The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. FDA

may be defined as Drugs that are not developed by the pharmaceutical industry for economic reasons but which respond to public health need.  Actually, the indications of a drug may also be considered as ' orphan ' since a substance may be used in the treatment of a frequent disease but may not have been developed for another, more rare indication. In fact, three cases may arise :  Products intended to treat rare diseases : These products are developed to treat patients suffering from very serious diseases for which no treatment, or at least a satisfactory one, has so far been available. These diseases affect only a small proportion of the population (less than one person per 2,000 in Europe), most often at birth or in infancy. The number of rare diseases for which no treatment is currently available is estimated to be between 4,000 and 5,000 world-wide. Twenty-five to 30 million people are reported to be affected by these diseases in Europe. Products withdrawn from the market for economic or therapeutic reasons : For example, thalidomide widely much used as a hypnotic drug some years ago and was then withdrawn from the market when its high teratogenic (triggering fetal malformations) risk was discovered. However this drug showed very interesting analgesic proprieties in diseases such as leprosy or lupus erythematosus. They are diseases for which no satisfactory treatment has been available. Products that have not been developed :either because they are derived from a research process that cannot be patented ; or because they concern important markets which are, however, not creditworthy (see the text Orphan drugs for Third-World countries). Orphanet About orphan drugs  Related term: rare diseases

orphan genes: Putative ORFs without any resemblance to previously determined protein- coding sequences…While theoretical evolutionary arguments support the reality of genes when homologues are found in a variety of distant species, this is not the case for orphan genes … Our results suggest that a vast majority of E. coli ORFs presently annotated as “hypothetical” correspond to bona fide genes. J Alimi et al “RT-PCR validation of 25 “orphan” genes” Genome Research 2000 Jul; 10 (7):  959- 966  Related terms: deorphaning,  deorphanizing, orphan proteins

orphan products: The Orphan Drug Act (ODA) provides for granting special status to a product /indication combination upon request of a sponsor, and if the product/indication combination meets certain criteria. This status is referred to as orphan designation. Orphan designation qualifies the sponsor of the product for the tax credit and marketing exclusivity incentives of the ODA. [FDA, US Orphan Product Designation, 2001]

outcomes research:  The terms "outcomes research" and "effectiveness research" have been used to refer to a wide range of studies, and there is no single definition for either that has gained widespread acceptance. As these fields evolved, it appears that "outcomes research" emerged from a new emphasis on measuring a greater variety of impacts on patients and patient care (function, quality of life, satisfaction, readmissions, costs, etc). The term "effectiveness research" was used to emphasize the contrast with efficacy studies, and highlighted the goal of learning how medical interventions affected real patients in "typical" practice settings (OTA, 1994). Effectiveness studies sought to understand the impact of health care on patients with diverse characteristics, rather than highly homogeneous study populations. While the terms may have different initial roots, there does not appear to be much value in distinguishing these activities, and the field is generally referred to as OER. .. OER evaluates the impact of health care (including discrete interventions such as particular drugs, medical devices, and procedures as well as broader programmatic or system interventions) on the health outcomes of patients and populations. OER may include evaluation of economic impacts linked to health outcomes, such as cost- effectiveness and cost utility. OER emphasizes health problem- (or disease-) oriented evaluations of care delivered in general, real- world settings; multidisciplinary teams; and a wide range of outcomes, including mortality, morbidity, functional status, mental well- being, and other aspects of health-related quality of life.   [Outcome of Outcomes Research at AHCPR: Final Report, Agency for Health Care Policy and Research, AHCPR Publication No. 99-R044] 

PAINS Pan Assay Interference Compounds: A true drug inhibits or activates a protein by fitting into a binding site on the protein.  Artefacts have subversive reactivity that masquerades as drug-like binding and yields false signals across a variety of assays.  These molecules. have defined structures, covering several classes of compounds. … But biologists and inexperienced chemists rarely recognize them. .. Time and research money are consequently wasted in attempts to optimize the activity of these compounds. Chemical con artists foil drug discovery, Jonathan Baell, Michael A. Walters, Nature  513: 481-483,  25 Sept 2014 doi: 10.1038/513481a 

patent cliff: A colloquialism to denote the potential sharp decline in revenues upon patent expiry of one or more leading products of a firm.

 “Investors are increasingly willing to accept that pharma companies can navigate the patent cliff through factors including growth in emerging markets, cost management, diversification and in some cases new drug launches,” said Deutsche Bank analyst Mark Clark “ Big pharma approaching bottom of patent cliff,, Nature Blog Oct 2012

patent pooling: A patent pool is an agreement between two or more patent owners to license one or more of their patents to one another or third parties.  A patent pool allows interested parties to gather all the necessary tools to practice a certain technology in one place, e.g, "one- stop shopping," rather than obtaining licenses from each patent owner individually. US Patent and Trademark Office "USPTO issues white paper on patent pooling" Jan. 19, 2001

patent stacking:  Taking out many patents for different aspects of a single innovation, thus forcing several royalty applications and payments. Aaron Cosbey , Sustainable Development Effects of the WTO TRIPS Agreement: A Focus on Developing Countries, International Institute for Sustainable Development, Canada, 2000 
Related term: royalty stacking

patent thickets: An overlapping set of patent rights requiring those seeking to commercialize new technology obtain licensees from multiple patentees.  Navigating the patent thicket, Carl Shapiro, Univ. of California, Berkeley, Mar. 2001

pathways:  A general term meant to include all forms of  molecular transactions and processes that are part of  biochemical systems. Some of these pathways may involve linear processing, but many involve complex branches, convergences, and even cycles. .... There are several different classes of biochemical pathways: metabolic pathways, signal transduction cascades, genetic networks, and drug metabolism pathways. In addition, protein interaction data  links protein data objects, and can therefore also be conceptualized as graphs. Although the relationship of  protein- interaction maps with biochemical pathways is undeniable, it is not obvious. ... the design of  adequate models for bio- process representation, manipulation and simulation is still a very open field of research. In conclusion, we will need to examine and discuss the relationships between all pathway information, protein interaction data, and biological process information in order to successfully produce informatics specifications for any of these kinds of  data.  Biopathways Consortium "Definition"

Pathway elucidation is critical,  in order to both identify the biochemical components in a pathway associated with disease, and the affect of a chemical entity on this pathway. This synergistic approach will help to identify ways to validate and prioritize targets, and enable us to understand the molecular mechanism of therapeutics.  The term biochemical pathways has principally referred to metabolic pathways, which are the pathways by which a cell converts compounds that enter it into cellular components (e.g., small molecules and macromolecules including proteins, nucleic acids, storage carbohydrates, and fatty acids) and by which the cell derives energy. Signaling pathways are biochemical pathways that regulate cellular characteristics and processes such as physiology, proliferation, changes in shape and motility, differentiation, adhesion, and intercellular interactions. High- content screening approaches can be used to help elucidate pathways.

PCR Polymerase Chain Reaction: A laboratory technique to rapidly amplify pre- determined regions of double- stranded DNA. Generally involves the use of a heat stranded DNA polymerase. IUPAC Bioinorganic

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double- stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult to isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [MeSH, 1991]

Originally described in 1984 by Kary B. Mullis, who shared the Nobel Prize for Chemistry for this invention in 1993, PCR enables the amplification of specific nucleotide sequences through the use of a DNA polymerase. The sequence to be amplified is identified through the use of synthetic oligonucleotides that are complementary to the two terminal regions of the targeted sequence.
Related terms: branched DNA, gene amplification, LCR Ligase Chain Reaction, NASBA.  Narrower terms: nested PCR, OLA, PNA Q-PCR, real time PCR, RT-PCR.

personalized medicine: The ability to offer the appropriate treatment to the right person, only when needed.

PGx: may be pharmacogenomics or pharmacogenetics.

pharmacoepidemiology: applies epidemiological methods to studies of the clinical use of drugs in populations. A modern definition of pharmacoepidemiology is: «the study of the use and effects/side-effects of drugs in large numbers of people with the purpose of supporting the rational and cost-effective use of drugs in the population thereby improving health outcomes… Pharmacoepidemiology may be drug-oriented, emphasizing the safety and effectiveness of individual drugs or groups of drugs, or utilization-oriented aiming to improve the quality of drug therapy through pedagogic (educational)  … Sophisticated utilization-oriented pharmacoepidemiology may focus on the drug (e.g. dose-effect and concentration-effect relationships), the prescriber (e.g. quality indices of the prescription), or the patient (e.g. selection of drug and dose, and comparisons of kidney function, drug metabolic phenotype/genotype, age, etc.). intervention. … The initial focus of pharmacoepidemiology was on the safety of individual drug products (pharmacosurveillance), but it now also includes studies of their beneficial effects. … Pharmacoepidemiological studies often make useful contributions to our knowledge about effectiveness and safety, because, unlike clinical trials, they assess drug effects in large, heterogeneous populations of patients over longer periods. Introduction to drug utilization research, WHO World Health Organization 2003

pharmacogenetics:  The study of existing genetic knowledge, and the generation of new genetic data, to understand and thus avoid DRUG TOXICITY and adverse effects from toxic substances from the environment.  MeSH 2004 

Pharmacogenetics and pharmacogenomics are frequently interchanged terms and can therefore be confused. For the purpose of clarity in the use of the terms in this review, pharmacogenetics is defined as the study of variability in drug responses attributed to hereditary factors in different populations. Pharmacogenomics is the determination and analysis of the genome (DNA) and its products (RNA and proteins) as they relate to drug response. For example, gene expression profiling using various microarray technologies has enabled the demonstration of distinct sub-sets of genes that may be expressed differentially in disease and healthy tissues. These genomic techniques can be useful for differential diagnosis of patients, particularly for heterogeneous diseases that present with similar clinical phenotypes but differ in molecular expression. Response to treatment can sometimes be recognized at the genomic level by tissue gene expression profiles. Expression profiles, however, differ from the approach of using inherited differences in our genetic information to predict responses to medicines, pharmacogenetics. Allen D. Roses; Pharmacogenetics, Human Molecular Genetics, Volume 10, Issue 20, 1 October 2001, Pages 2261–2267,

A subset of pharmacogenomics encompassing the study of genetic variation underlying differential response to drugs, particularly genes involved in drug metabolism.  With the implementation of pharmacogenetics, diseases will be evaluated by mechanisms, rather than just symptoms, and early response will be based on prognosis and susceptibility rather than just diagnosis. It will introduce a bottom- up approach to disease, which will be defined in terms of its heterogeneity, and not "averaged out" to conform to a uniform model. 

pharmacogenomics:   Comprises the study of variations in targets or target pathways, variation in metabolizing enzymes (pharmacogenetics) or, in the case of infectious organisms, genetic variations in the pathogen. CHI Drug Discovery Map

Pharmacogenomics is the analysis of the effect of genomics — in particular, genetic variation (polymorphisms) — on drug response. This practice can potentially help clinicians administer more tailored treatment. The term pharmacogenetics is often used to refer specifically to tests that predict drug response; however, the terms pharmacogenetics and pharmacogenomics are often used interchangeably. 

Can be construed as the study of the entire complement of pharmacologically relevant genes, how they manifest their variations, how these variations interact to produce phenotypes, and how these phenotypes affect drug response. A key element of pharmacogenomics is, not surprisingly, the large- scale and high throughput collection of data, including DNA sequence variations, mRNA expression analysis, enzyme kinetic assays, and cellular localization experiments. Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Annual Review of Pharmacology & Toxicology 2002  

The study of how an individual's genetic inheritance affects the body's response to drugs and holds the promise that drugs might one day be tailor- made for individuals and adapted to each person's own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person's response to medicines, but understanding an individual's genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.  Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genes, proteins, and single nucleotide polymorphisms. Human Genome Project Information, Pharmacogenomics, Oak Ride National Lab, 2001

From pharmacology + genomics.  Alternatively: individualized medicine, personalized medicine, pharmacoproteomics

pharmacovigilance:   The aims of pharmacovigilance are to enhance patient care and patient safety in relation to the use of medicines, especially with regard to the prevention of unintended harm from the use of drugs; to improve public health and safety in relation to the use of medicines by the provision of reliable, balanced information resulting in more rational use of drugs; and to contribute to the assessment of the risk-benefit profile of medicines, thus encouraging safer and more effective use of medicines and a resolution of the  sometimes apparently conflicting interests of public health and individual patient welfare. WHO 2006 

The process of (a) monitoring medicines as used in everyday practice to identify previously unrecognised or changes in the patterns of their adverse effects; (b) assessing the risks and benefits of medicines in order to determine what action, if any, is necessary to improve their safe use; (c) providing information to users to optimise safe and effective use of medicines; (d) monitoring the impact of any action taken. Medicines Control Agency, UK, Pilot publication scheme, Glossary of terms, 2003  Related terms: Phase IV/postmarketing surveillance

pharming: Use of  transgenic animals to produce drugs in their milk, urine or eggs.  Transgenic plants can also be used. (Tobacco is said to be particularly amenable to this application).  

Phase IV/ postmarketing surveillance: At this stage, after a drug has been launched, pharmaceutical companies may conduct further studies of its performance, often examining long- term safety. 

Phase zero, Phase O: Phase 0 studies are exploratory studies that often use only a few small doses of a new drug in a few patients. They might test whether the drug reaches the tumor, how the drug acts in the human body, and how cancer cells in the human body respond to the drug. The patients in these studies might need extra tests such as biopsies, scans, and blood samples as part of the study process.The biggest difference between phase 0 and the later phases of clinical trials is that there’s almost no chance the volunteer will benefit by taking part in a phase 0 trial – the benefit will be for other people in the future. Because drug doses are low, there’s also less risk to the patient in phase 0 studies compared to phase I studies. Phase 0 studies help researchers find out whether the drugs do what they’re expected to do. If there are problems with the way the drug is absorbed or acts in the body, this should become clear very quickly in a phase 0 clinical trial. This process may help avoid the delay and expense of finding out years later in phase II or even phase III clinical trials that the drug doesn’t act as expected to based on lab studies. Phase 0 studies aren’t used widely, and there are some drugs for which they wouldn’t be helpful. Phase 0 studies are very small, often with fewer than 15 people, and the drug is given only for a short time. They’re not a required part of testing a new drug. American Cancer Society, Phase Zero Clinical trials  Related terms: microdosing

phenotypic screens: look at the effects, or phenotypes, that compounds induce in cells, tissues or whole organisms … Beginning in the 1980s, advances in molecular biology and genomics led to phenotypic screens largely being replaced by screens against defined targets implicated in disease.… some researchers have concluded that reductionist approaches such as target-based screening are useful but may also limit the breadth of new findings. Phenotypic screening, take two Kotz, J.SciBX 5(15); doi:10.1038/scibx.2012.380 Published online April 12 2012  Compare targeted based drug discovery, screens

pipelines: The process of drug development has evolved into an extremely complex procedure. The average drug takes 12 years and $270 million from initial discovery to public usage.(1) For every drug that is deemed marketable by the FDA, thousands of others are considered either unsafe or ineffective clinically. Beginning with preclinical research, new chemical entities (NCEs) are discovered in laboratories and tested in animals for safety and biological activity. If a compound is thought to be safe and effective as a chemical agent, a pharmaceutical company then submits an investigational new drug application (NDA) to the FDA. Once approved for clinical studies, a three-phase process begins where safety and efficacy are continually assessed with increased scrutiny and an increasing patient population. Approximately 70% of drugs entering clinical trials complete Phase I, 33% complete Phase II, and 27% complete Phase III. After Phase III is completed a company then submits a NDA to the FDA. Those drugs that are approved for marketing comprise an extremely small percentage of new chemical entities (NCEs) that are tested. In fact, from thousands only a handful of drugs undergo clinical studies, and even fewer receive market approval. C. Daniel Mullins et. al. " Projections of drug approvals, patent expirations and generic entry from 2000 to 2004" report prepared for the Dept. of Health and Human Services' Conference on Pharmaceutical Pricing Practices, Utilization and Costs August 8- 9, 2000, Washington DC, US

portfolio management:  For many pharmaceutical companies, much of the focus in managing portfolio risk has focused on R&D choices for pipeline products, as well as research portfolio choices on the drug discovery side. In addition to these levers, there is significant opportunity for pharmaceutical companies to manage risk through smarter investment in life- cycle management. These investments span a variety of functions from legal to sales and marketing to R&D. In the R&D area, some of the key investments include clinical studies and investments in formulation sciences and drug delivery. Managing Product Risk through Life- Cycle Management, Dr. Philip Ma, Partner, McKinsey & Co.Related term: life cycle management

post-genomic:  The genome era is generally regarded to have started on 28 July 1995, with the publication of the genome of the bacterium Haemophilus influenzae. ["A point of entry into genomics" Nature Genetics 23:273 Nov. 1999] But the human mitochondrial genome was sequenced in 1981 and published in Nature 290 (5806): 457- 465, Apr. 9, 1981. Sequence and organization of the human mitochondrial genome by S. Anderson et. al.

With an increasing number of organisms for which we have (more or less) complete genomes we are beginning to see glimpses of the power of having fully mapped sequences. Still, in most contexts talk about being "post- genomic" seems a little premature. "Post Mendelian" seems more accurate as we move from an era in which genetics has been rooted in monogenic diseases with high penetrance to a greater awareness (but limited understanding) of polygenic diseases (and traits) often with relatively low penetrance.

preclinical drug evaluations: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.  MeSH, 1974

preclinical investigations: Laboratory and animal studies designed to test the mechanisms, safety, and efficacy of an intervention prior to its applications to humans [IRB]

precompetitive research: Several issues need to be resolved in order to establish a collaborative consortia from the pharmaceutical company perspective. A major challenge is defining the domain of precompetitive research. The basic biology, the understanding of disease, biomarkers of prognosis, and even drug responses all can be areas of precompetitive R&D, Power said. Pharmaceutical companies have recognized that they cannot develop a full understanding of these different facets of drug development on their own. Establishing Precompetitive Collaborations to Stimulate Genomics-Driven Product Development: Workshop Summary. 2011

predictive ADME: The completion of the Human Genome Project and recent advances in our understanding of the molecular mechanisms of diseases have provided increasing numbers of newly defined biological pathways and networks with potential preventive or therapeutic targets. The development of molecular diversity libraries and screening of these libraries have provided tremendous opportunities to discover new chemical and biological agents for the prevention and treatment of diseases. This created the belief that increasing numbers of new molecular entities would enter clinical testing and would receive approval from the Food and Drug Administration (FDA) to treat human disorders. However, this has not occurred. Many candidate agents are failing during clinical testing because of their unfavorable pharmacokinetic properties, unacceptable adverse effects, or major toxicities, as well as the lack of efficacy.

The safety of each new chemical entity must be demonstrated prior to its entry into clinical trials. Investigational New Drug (IND) applications to the FDA require chemistry, manufacturing, and control information and results from preclinical toxicology studies for the safety of new agents. Results of nonclinical pharmacokinetic studies for defining ADME properties, addressing important safety issues, or assisting the evaluation of toxicology data for investigational new agents are highly desirable in IND submissions. Novel preclinical tools for Predictive ADME-Toxicology RFA Number: RFA-RM-04-023, 2004 

predictive safety: Unexpected toxicity is the single greatest cause of pipeline attrition. Despite the fact that a typical preclinical safety program will consume about 1,300 rats and 90 dogs, there is no guarantee that the compound will not present safety problems serious enough to warrant termination.

productivity:  Iain Cockburn, a professor at the Boston University School of Management who has extensively studied pharmaceutical research productivity, believes the current dearth of new drugs is merely an inevitable pause in the industry's development cycle. Today's drug deficit is often compared with a golden age of applications in the early 1990s that were spawned by advances in small- molecule chemistry 15 to 20 years earlier, he says. Now the industry is adjusting to a new era of molecular biology that will take time to produce results. The adjustment, Cockburn suggests, was side- tracked somewhat by the 1990's biotechnology boom, which confused the process of drug development as large pharmaceutical firms and biotech companies sorted out their roles as potential rivals and collaborators. Further, he says, it is simply harder to invent new drugs now, because the low- hanging fruit -- such as the once- revolutionary ace inhibitors -- has already been plucked. "Now the industry is focusing on cancer, Alzheimer, and exotic viruses. They're working on tougher problems," he says. "The way you come up with these drugs is through a lot of heavy- duty science rather than industrial chemistry, and it's just a lot more expensive."  Susan Warner, Pipeline Anxiety: Scientists Pumped into New Roles, Scientist, 17 (10) May 19, 2003 

proof of concept:  Although not suggested by natural language, and in contrast to usage in other areas, Proof of Principle and Proof of Concept are not synonymous in drug development. A third term, Proof of Mechanism, is closely related and is also described here. All of these terms lack rigorous definitions and exact usage varies between authors, between institutions and over time. The descriptions given below are intended to be informative and practically useful.[citation needed] The underlying principle is related to the use of biomarkers as surrogate endpoints in early clinical trials. See for example the introductory discussion on pages 3 to 9 of Downing's Biomarkers and surrogate endpoints: clinical research and applications.[6] In early development it is not practical to directly measure that a drug is effective in treating the desired disease, and a surrogate endpoint is used to guide whether or not it is appropriate to proceed with further testing. For example, although it cannot be determined early that a new antibiotic cures patients with pneumonia, early indicators would include that the drug is effective in killing bacteria in laboratory tests, or that it reduces temperature in infected patients - such a drug would merit further testing to determine the appropriate dose and duration of treatment. A new antihypertension drug could be shown to reduce blood pressure, indicating that it would be useful to conduct more extensive testing of long-term treatment in the expectation of showing reductions in stroke (cerebrovascular accident) or heart attack (myocardial infarction). Surrogate endpoints are often based on laboratory blood tests or imaging investigations like X-ray or CT scan.[citation needed]  ...  refers to early clinical drug development, conventionally divided into Phase I and Phase IIa.  Wikipedia  accessed 2018 Feb 5   

Compare proof of principle. Proof of concept is certainly more prevalent as a term.  Google 2018 Sept 10 Proof of concept over 21 Million, proof of principle over 6 Million, 3 ½ times as many for proof of concept.  These two terms are sometimes used interchangeably, though proof of concept seems generally earlier than proof of principle.  While many of the above examples have a financial context these terms are also used in more basic research.

Proof of Mechanism or PoM relates to the earliest stages of drug development, often pre-clinical (i.e., before trialling the drug on humans, or before trialling with research animals). It could be based on showing that the drug interacts with the intended molecular receptor or enzyme, and/or affects cell biochemistry in the desired manner and direction.

proof of principle:  Proof of Principle studies are an early stage of clinical drug development when a compound has shown potential in animal models and early safety testing. This step of proof-of-principle (PoP) or proof-of-concept (PoC) often links between Phase-I and dose ranging Phase-II studies. These small-scale studies are designed to detect a signal that the drug is active on a pathophysiologically relevant mechanism, as well as preliminary evidence of efficacy in a clinically relevant endpoint. Sponsors use these studies to estimate whether their compound might have clinically significant efficacy in other diseases states. Proof of Principle studies, Schmidt B.  Epilepsy Res. 2006 Jan;68(1):48-52.   Compare proof of concept

protein expression:  Protein expression analysis is undergoing a technological revolution, which will change the fundamental nature of the data available. ... Current methods for measuring protein expression are very different from those for measuring gene expression. Typically, 2D gels are used to separate the proteins from one another, and mass spectrometry (MS) is then applied to identify the proteins. MS provides remarkably specific identification of protein fragments, based on their masses. The masses are then compared with lists of computed masses for identification. More and more groups are now seeking to bypass 2D gels, using combinations of protein chips, liquid chromatography, capillary electrophoresis, and mass spectrometry for protein analysis.

proteomics:  The analysis of complete complements of proteins. Proteomics includes not only the identification and quantification of proteins, but also the determination of their localization, modifications, interactions, activities, and, ultimately, their function. Initially encompassing just two- dimensional (2D) gel electrophoresis for protein separation and identification, proteomics now refers to any procedure that characterizes large sets of proteins. The explosive growth of this field is driven by multiple forces - genomics and its revelation of more and more new proteins; powerful protein technologies, such as newly developed mass spectrometry approaches, global [yeast] two- hybrid techniques, and spin-offs from DNA arrays; and innovative computational tools and methods to process, analyze, and interpret prodigious amounts of data. Stanley Fields "Proteomics in Genomeland" Science 291: 1221-1224 Feb. 16, 2001

rational drug discovery: In contrast to traditional methods of drug discovery (known as forward pharmacology), which rely on trial-and-error testing of chemical substances on cultured cells or animals, and matching the apparent effects to treatments, rational drug design (also called reverse pharmacology) begins with a hypothesis that modulation of a specific biological target may have therapeutic value. In order for a biomolecule to be selected as a drug target, two essential pieces of information are required. The first is evidence that modulation of the target will be disease modifying. This knowledge may come from, for example, disease linkage studies that show an association between mutations in the biological target and certain disease states.[15] The second is that the target is "druggable". This means that it is capable of binding to a small molecule and that its activity can be modulated by the small molecule.[16] Once a suitable target has been identified, the target is normally  cloned  and  produced and purified. The purified protein is then used to establish a screening assay. In addition, the three-dimensional structure of the target may be determined.  The search for small molecules that bind to the target is begun by screening libraries of potential drug compounds. This may be done by using the screening assay (a "wet screen"). In addition, if the structure of the target is available, a virtual screen may be performed of candidate drugs. Ideally the candidate drug compounds should be "drug-like", that is they should possess properties that are predicted to lead to oral bioavailability, adequate chemical and metabolic stability, and minimal toxic effects.[17] Several methods are available to estimate druglikeness such as Lipinski's Rule of Five and a range of scoring methods such as lipophilic efficiency.[18] Several methods for predicting drug metabolism have also been proposed in the scientific literature.[19] Due to the large number of drug properties that must be simultaneously optimized during the design process, multi-objective optimization techniques are sometimes employed.[20] Finally because of the limitations in the current methods for prediction of activity, drug design is still very much reliant on serendipity[21] and bounded rationality.[22] Wikipedia accessed 2018 Sept 10   
Related terms
: structure based drug design   Combinatorial Libraries & synthesis: rational library design,  computational quantum chemistry

recombinant DNA technology: A body of techniques for cutting apart and splicing together different pieces of DNA. When segments of foreign DNA are transferred into another cell or organism, the substance for which they code may be produced along with substances coded for by the native genetic material of the cell or organism. Thus, these cells become "factories" for the production of the protein coded for by the inserted DNA.  [NIGMS]  Related terms:  biotechnology, gene disruption, gene manipulation, genetic engineering

regenerative medicine: A field of medicine concerned with developing and using strategies aimed at repair or replacement of damaged, diseased, or metabolically deficient organs, tissues, and cells via TISSUE ENGINEERING, CELL TRANSPLANTATION; and ARTIFICIAL ORGANS and BIOARTIFICIAL ORGANS and tissues.  MeSH 2004 

research tools: We use the term "research tool" in its broadest sense to embrace the full range of resources that scientists use in the laboratory, while recognizing that from other perspectives the same resources may be viewed as "end products." For our purposes, the term may thus include cell lines, monoclonal antibodies, reagents, animal models, growth factors, combinatorial chemistry libraries, drugs and drug  targets, clones and cloning tools (such as PCR), methods, laboratory equipment and machines, databases and computer software. .. NIH Working Group on Research Tools, June 4, 1998   Related term: pre-competitive

resourceome:  Biologist users and scientists approaching the field do not have a comprehensive index of bioinformatics algorithms, databases, and literature annotated with information about their context and appropriate use. We suggest that the full set of bioinformatics resources—the “resourceome”—should be explicitly characterized and organized. A hierarchical and machine-understandable organization of the field, along with rich cross-links (an ontology!) would be a useful start. "Time to organize the bioinformatics resourceome" Nicola Cannata, Emanuela Merelli, Russ B. Altman*,  PLOS Computational Biology, Dec. 2005  DOI: 10.1371/journal.pcbi.0010076

ridiculome: What does it take to turn a ridiculome into a relevantome? Quality control metrics (recall/precision)  Context specificity   Cellular: Is the interaction specific to a cellular phenotype?    Molecular: Is the interaction dependent on the availability of other molecular species
Links to data (and literature) Links to analysis of biomedical problems/ Focus on specific features (e.g. mechanisms)  MAGNet Center: Andrea Califano, NCIBI: Brian Athey, Simbios: Russ Altman, Creating a DBP Community to Enhance the NCBC Biomedical Impact, NCBC Work Group Report, 18 July 2006

RNAi RNA interference: A gene silencing phenomenon whereby specific dsRNAs ( RNA, DOUBLE- STRANDED) trigger the degradation of homologous mRNA ( RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA- INDUCED SILENCING COMPLEX (RISC). DNA METHYLATION may also be triggered during this process. MeSH 2003 Broader term: gene silencing

robust: A statistical test that yields approximately correct results despite the falsity of certain of the assumptions on which it is based  Oxford English Dictionary 

Hence, can refer to a process which is relatively insensitive to human foibles and variables in the way (for example, an assay) is carried out. Idiot- proof.

rules of five: Lipinski’s rules. Set of criteria for predicting the oral bioavailability of a compound on the basis of simple molecular features  (molecular weight,  CLogP, numbers of  hydrogen- bond donors and acceptors). Often used to profile a library or virtual library with respect to the proportion of drug- like members  which it contains. IUPAC Combinatorial

An algorithm, developed  by Christopher A. Lipinski (of Pfizer) and colleagues, in which many of the cutoff numbers are five or multiples of five. There are actually four rules, and Pfizer has developed a additional number of criteria for adoption of lead candidates. Advanced Drug Delivery Research 23: 3- 25, 1997.

safety pharmacology: Pharmacology studies can be divided into three categories: primary pharmacodynamic, secondary pharmacodynamic, and safety pharmacology studies. For the purpose of this document, safety pharmacology studies are defined as those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. ICH Guidance for Industry, S7A Safety Pharmacology Studies for Human Pharmaceuticals,  2001

sample preparation:  The discussants concluded that the issue of sample preparation and purification has been sadly neglected at most meetings dealing with proteomics. There was the impression among some of the discussants that protein biochemists were developing and using methods to purify proteins that were not being adequately defined compositionally by mass spectrometrists interested in proteins. Defining the Mandate of Proteomics in the Post- Genomics Era, National Academy of Sciences, 2002

Sample prep isn't the sexiest job around, but it is one of the most critical. The quality of isolated nucleic acid and protein samples is critical to generating accurate and informative data. As genomic and proteomic technologies move in the direction of higher throughput, upstream sample preparation becomes a potential bottleneck. Sample capture, transportation, storage, and handling are as critical as extraction and purification procedures. Obtaining homogenous samples or isolating individual cells from clinical material is imperative. Standards are essential. Advances in microfluidic and microarray technologies have further amplified the need for higher throughput, miniaturized, and automated sample preparation processes.

scaffold hopping:  the definition of scaffold hopping and, more importantly, the detection of what constitutes a scaffold hop, is also ill-defined and highly subjective. Essentially, it is agreed that scaffolds should be substantially different from each other, although significantly similar to each other, to constitute a hop. In the latter, the scaffolds must permit a similar geometric arrangement of functional groups to permit the mode of action. However, this leaves the paradox of how to describe both scaffold similarity and dissimilarity simultaneously. In this paper, the current statuses of scaffolds and scaffold hopping are reviewed based on published examples of scaffold hopping from the literature. An investigation of the degree to which it is possible to formulate a more rigorous definition of scaffolds and hopping in the context of molecular topologies is considered. N Brown, E Jacoby, On scaffolds and hopping in medicinal chemistry. Mini Rev Med Chem 6 (11) :1217- 1229, Nov 2006 

scalable:   Capable of being industrialized and expanded for high- throughput. Analogous to recipes optimized for large groups, rather than standard recipes being quadrupled or more, with less than ideal results. Also spelled scaleable.

self-assembly: <biology>  A process in which supramolecular hierarchical organization is established without external intervention.... The approaches used can be expected to fall into two general categories. The first involves directly mimicking biological systems or processes to produce materials with enhanced properties. An example of this approach is the use of molecular genetic techniques to produce polymers with unprecedentedly uniform molecular length. The second category involves studying how nature accomplishes a task or creates a structure with unusual properties, and then applying similar techniques in a completely different context or using completely different materials. [Biomolecular self- assembling materials, National Academy of Sciences 1996]  Narrower terms: self- assembling biomolecular materials, self-assembling peptides. Related terms: nanoscience

Sentinel Initiative: On May 22, 2008, FDA launched the Sentinel Initiative with the ultimate goal of creating and implementing the Sentinel System--a national, integrated, electronic system for monitoring medical product safety. The Sentinel System will enable FDA to query multiple, existing data sources, such as electronic health record systems and medical claims databases, for information about medical products. The system will enable FDA to query data sources at remote locations, consistent with strong privacy and security safeguards.  Data sources will continue to be maintained by their owners.  This historic new system will strengthen FDA's ability to monitor the performance of a product throughout its entire life cycle. FDA, US 

sexy technologies: What makes technologies sexy? It seems to be a combination of being new, innovative and challenging, affording clever people a chance to learn new skills (and demonstrate how competitive and bright they are) and expensive (or otherwise not available to just anyone). A quick Google search identified artificial intelligence, fuel cells, high- speed computers, robotics, nanotechnology, Java, smart cards, wireless communications and biomaterials as "sexy" by some criteria. I'd be interested to hear other interpretations and nuances of this class of technologies. Are there significant differences in what biologists, businesspeople, chemists, computer scientists and others consider "sexy technologies"? 

single molecule detection: Recent advances in optical imaging and biomechanical techniques have demonstrated that it is possible to make observations on the dynamic behavior of single molecules, to determine mechanisms of action at the level of an individual molecule, and to explore heterogeneity among different molecules within a population. These studies have the potential to provide fundamentally new information about biological processes and are critical for a better understanding of cellular function. ...  Single molecule methods are likely to lead to significant advances in understanding molecular movement, dynamics, and function. NIGMS, NICDC, NHGRI, Single Molecule Detection and Manipulation, Feb. 12, 2001  Broader terms: attomole, femtomole, micromole, nanomole, picomole, ultrasensitivity, yocto, zeptomole

small molecules: Preferred for drugs as they are orally available (unlike proteins which must be administered by injection or topically). Size of small molecules is generally under 1000 Daltons, but many estimates seem to range between 300 to 700 Daltons.

SNP Single nucleotide polymorphism: SNPs are single base pair positions in genomic DNA at which different sequence alternatives (alleles) exist in normal individuals in some population(s), wherein the least frequent allele has an abundance of 1% or greater.  Thus single base insertion/ deletion variants (indels) would not formally be considered to be SNPs. ... In practice, the term SNP is typically used more loosely than required by the above definition. ... Complications with the above definition also exist. Specifically, some people might not want to consider disease predisposing single base variants to be SNPs - but the above definition would encompass such things as recessively acting, low penetrance, dominant, quantitative trait loci, or risk associated alleles, since all of these will occur in some normal (non- diseased) individual.  Also the 'some population' component of the definition is limited by practical challenges of attaining and surveying representative global population samples. Consequently, claims of non- polymorphic sequences should always be accompanies by statements of the actual populations and the numbers of chromosomes tested. Overall, it is therefore apparent that the term 'SNP' is being widely and imprecisely used as a catch- all label for many different types of subtle sequence variation. Anthony Brooks "The essence of SNPs" Gene 234: 177-186, 1999 .

The most common form of DNA variation, alterations to a single base. If the SNP is in a gene, it can disrupt the gene's function. Most SNPs do not occur in genes, but can be associated with other types of DNA variation and so are used effectively as markers.

A SNP is a position in the genome where some individuals have one DNA base (e.g., A), and others have a different base (e.g., C). SNPs and point mutations are structurally identical, differing only in their frequency. Variations that occur in 1% or less of a population are considered point mutations, and those occurring in more than 1% are SNPs. This distinction is pragmatic and reflects the fact that low- frequency mutations cannot be used effectively in genetic studies as genetic markers, while more common ones can. 

SNPs can occur in coding regions of the genome (cSNPs), in regulatory regions (rSNPs), or, most commonly, in "junk DNA" regions, in which case they are referred to as anonymous SNPs. 
Narrower terms: SNPs- human,;
  anonymous SNPs, cSNPs, candidate SNP, exonic SNPs, intron SNPs, pSNP, promoter SNPs, rSNP, SNP haplotypes, synonymous SNP.  
Related terms: idiomorphism, protein polymorphisms,  single amino acid polymorphisms SAAPS, SNP Consortium, SNP discovery, SNP scans

specialty pharmaceuticals: Every health plan, institution, medical group, pharma/biotech company and PBM seems to have its own definition, but specialty pharmaceuticals are generally understood to be medications that are:* Injectable.  * Indicated for the treatment of chronic -- and often rare -- illnesses. * Expensive -- a single therapy can cost anywhere from $5,000 to $350,000 per patient per year.  That's the simple definition. Beyond these three points, there are a few additional characteristics that usually apply to specialty pharmaceuticals:  Non-oral administration. Specialty drugs are almost always administered by non-oral means (such as injection or infusion).  Biological origin. Many specialty products (such as blood products and gene-based therapies) are manufactured with a biological basis by biotech companies, or by traditional pharmaceutical companies through biotech divisions or through business partnerships with biotech companies.  Non-hospital administration. Usually, specialty products are administered in a non-hospital setting (such as a physician's office, a clinic or the patient's home). Reimbursement via the medical benefit. In managed care, specialty drugs are typically managed and reimbursed outside of the pharmacy benefit, usually through the medical benefit.  Special requirements. Specialty medications usually require special storage and handling (such as refrigeration). They also demand comprehensive patient education and require continuous monitoring.  The world of specialty pharma A look at the value and growth of specialty products Jun 01, 2005   Tony Pinsonault

spheroids and 3d cell  culture: It’s been well established that culturing cells in three-dimensions is much more representative of the in vivo environment than traditional two-dimensional cultures. The multicellular arrangement allows cells to interact with each other and the extracellular matrix (ECM), providing a much better understanding of cellular complexities, particular in cancer and stem cell research  Thermo Fisher, Brief History of Spheroids

stealth patents: Beware of submarine- stealth genetic patents, they can be deadly for scientific research. That was the consensus of genetic patent experts Monday at CHI's Genome Tri-Conference The biggest enemy of scientific progress, the experts said, are so- called "stealth" patents -- those which are filed on genes that researchers have located, but haven't discovered their function. They sit on the patent, sometimes for long periods of time, during which no research is done. In January [2001], the U.S. Patent and Trademark Office finalized guidelines forbidding stealth patenting, but finding these patents will be a long process. Kristen Philipkowski "New Quest: Mapping Gene Patents" Wired, Mar 6, 2001

Patents filed on genes which have been discovered but have unknown function(s). Also known as submarine patents

stem cell transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types. MeSH 2003

stem cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. Includes Fibroblasts, Hematopoietic Stem Cells, Erythroid Progenitor Cells, Tumor Stem Cell  MeSH, 1984 
Narrower terms: embryonic stem cells, hematopopoietic stem cells.  
Stem Cell Glossary, NIH, 2016
Stem cell research funding
, NIH 

strategic alliances:
  As the first decade of the 21st century comes to an end, the pharmaceutical industry is facing a major revenue downturn.  The contributing factors are the expiration of patents on a number of blockbuster drugs and the stagnant productivity of R&D.  As a consequence generics are expected to seriously erode revenues and the introduction of new proprietary drugs is not adequate.  The once insular pharmaceutical industry has been forced to look outside beyond its walls for drug pipeline candidates.  The result has been an almost expediential growth of the past decade in the number and value of strategic alliances. Insight Pharma Reports
Strategic Alliances: Synergistic Path to Value Creation 2010

Alliances are not always as strategic as hoped.

strategic investors: affiliates of corporations that invest on behalf of their parent company STRATEGIC VS. TRADITIONAL INVESTORS: THE LOWDOWN FROM A VENTURE CAPITAL VET,PAUL H. LEE, Fast Company Oct 8 2009 1392582/strategic-vs- traditional-investors-lowdown- venture-capital-vet 
Also known as “strategics”. Many big pharmaceutical companies now have venture capital arms.

structural genomics: The discipline of determining protein structures. It adds critical information in at least two points in the drug discovery pathway: (1) target identification, or selecting a pathway in which a drug might function, and (2) medicinal chemistry, or the actual design of compounds to modulate this pathway.  As traditionally defined, the term structural genomics referred to the use of sequencing and mapping technologies, with bioinformatic support, to develop complete genome maps (genetic, physical, and transcript maps) and to elucidate genomic sequences for different organisms, particularly humans. Now, however, the term is increasingly used to refer to high- throughput methods for determining protein structures. 

structural variants: No two genomes are alike; instead, each displays structural variability in the form of single-nucleotide polymorphisms (SNPs), deletions or insertions of various sizes, which are collectively called copy number variants (CNVs) and inversions, which are copy number neutral structural variants.  Nicole Rusk, Finding copy-number variants, Nature Methods 5(11):917 Nov 2008

Structure Activity Relationship (SAR): The relationship between chemical structure and pharmacological activity for a series of compounds. IUPAC Medicinal Chemistry

structure based design: A design strategy for new chemical entities based on the three- dimensional (3D) structure of the target obtained by X-ray or nuclear magnetic resonance (NMR) studies, or from protein homology models. IUPAC Computational

structure based drug design: Structure-based design (SBD) has been in use within the pharmaceutical industry for over twenty-five years. SBD of compound properties are still developing and growing in acceptance.. 

synchrotrons: Devices for accelerating protons or electrons in closed orbits where the accelerating voltage and magnetic field strength varies (the accelerating voltage is held constant for electrons) in order to keep the orbit radius constant. MeSH, 1993

An important alternative to x-ray crystallography for solving protein structures.

synthetic biology: Synthetic biology an interdisciplinary branch of biology and engineering.  The subject combines disciplines from within these domains, such as biotechnologygenetic engineeringmolecular biologymolecular engineeringsystems biologybiophysicselectrical engineeringcomputer engineeringcontrol engineering and evolutionary biology. Synthetic biology applies these disciplines to build artificial biological systems for research, engineering and medical applications…. Synthetic biology is seen differently by biologists and engineers. Originally seen as part of biology, in recent years the role of electrical and chemical engineering has become more important. As usage of the term has expanded, synthetic biology was recently defined as the artificial design and engineering of biological systems and living organisms for purposes of improving applications for industry or biological research.[7]  In general its purpose can be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.  Wikipedia accessed 2018 Feb 27

Synthetic biology news & research, Nature

systems biology: is based on the understanding that the whole is greater than the sum of the parts.

Systems biology has been responsible for some of the most important developments in the science of human health and environmental sustainability. It is a holistic approach to deciphering the complexity of biological systems that starts from the understanding that the networks that form the whole of living organisms are more than the sum of their parts. It is collaborative, integrating many scientific disciplines – biology, computer science, engineering, bioinformatics, physics and others – to predict how these systems change over time and under varying conditions, and to develop solutions to the world’s most pressing health and environmental issues.  This ability to design predictive, multiscale models enables our scientists to discover new biomarkers for disease, stratify patients based on unique genetic profiles, and target drugs and other treatments.  Institute for systems biology

target: Molecules in the body that may be addressed by drugs to produce a therapeutic effect. (Also used to refer to the material -- DNA or RNA - that one exposes to the probes on a microarray so that hybridization can be measured subsequently.
Narrower terms: target characterization, target glut, target identification, target screening, target validation.  Related terms: gene function, protein function, antisense, hit, lead

target identification: Target identification methods  provide a finer degree of detail than target screening and require evidence that the gene/ protein is correlated with the disease. 

target validation: Demonstrating that a molecular target is critically involved in a disease process, and that modulation of the target is likely to have a therapeutic effect. Determining which among genes or proteins being investigated as potential drug targets lead to phenotypic changes when modulated, suggesting that they may have value as therapeutic targets. Many people would say a target is truly validated only after proven effective in human trials.  The definition of target validation is clearly evolving, can be seen as "slippery" and clearly means different things to different people. 

text mining: Using data mining on unstructured data, such as the biomedical literature.  

Text Mining Glossary, ComputerWorld, 2004   Includes Categorization, clustering, extraction, keyword search, natural language processing, taxonomy, and visualization.

tissue engineering:  Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. A cell culture facility is required for cell harvest and expansion. MeSH, 2002

The term "tissue engineering" was coined at an NSF [National Science Foundation] -sponsored meeting in 1987. At a later NSF- sponsored workshop, tissue engineering was defined as "...the application of principles and methods of engineering and life sciences toward fundamental understanding ...and development of biological substitutes to restore, maintain and improve [human] tissue functions." This definition is intended to include procedures where the biological substitutes are cells or combinations of different cells that may be implanted on a scaffold such as natural collagen or as synthetic, biocompatible polymers to form a tissue. ["Tissue Engineering" National Science Foundation]

top-down: A systems approach, which looks at the big picture and complexity. Genomics is essentially a top- down approach, the opposite of a bottom- up approach. Our ways of thinking have been so profoundly influenced by bottom- up, reductionist approaches that we are having to learn to think in very different ways to begin to fully exploit genomic data

toxicogenetics: The study of existing genetic knowledge, and the generation of new genetic data, to understand and thus avoid DRUG TOXICITY and adverse effects from toxic substances from the environment. MeSH 2004

toxicogenomics: In its strictest definition, refers to the use of DNA microarray technology to identify patterns of gene expression that can be used to predict human toxicity of new drug candidates or other potential toxicants. The concept is based on the hypothesis, proven in only a preliminary sense, that a finite and limited set of such patterns, or signatures, exists and that these signatures are, in fact, highly predictive

translational medicine: Recent advances in biological understanding are allowing pharmaceutical companies to begin to develop tailored therapeutics, thereby allowing patients to receive the right drug, at the right dose, and at the right time. However, in order for such treatments to be developed, companies need to be able to better link data from the laboratory to the clinic (bench to bedside). This concept is frequently referred to as translational medicine.  Semantic Web Health Care and Life Sciences SIG Charter, 2008 
Related terms: clinical proteomics, molecular medicine, translational research 

translatome: The cellular population of proteins expressed in the organism at a given time, explicitly weighted by their abundance. ... Our definition of the translatome is partially motivated by the ambiguities in term proteome, which has two competing definitions. First, broadly favoured by computational biologists, is a list of all the proteins encoded in the genome (Gaasterland 1999, Doolittle 2000). In this context, it is equivalent to what some refer to as the ORFeome, i.e. the set of genes excluding non- coding regions. Experimentalists, especially those involved in large- scale experiments such as expression analysis and 2D electrophoresis, favor a second definitions. Here it is used to describe the actual cellular contents of proteins, taking into account the different levels of protein concentrations (Yates 2000). We prefer the former definition for proteome, and use the term translatome for the later.  Dov Greenbaum "Interrelating Different Types of  Genomic Data" Dept. of Biochemistry and Molecular Biology, Yale Univ. 2001  

truth: Making new technology work may be easier than using it to discover truth. Roger Brent, "Functional genomics: learning to think about gene expression data" Current Biology 9: R338- R341, 1999

Question from Nature column Lifelines put to Michel Brunet, palaeontologist "What is the one thing about science you wish the public understood better?" Answer "That the 'truth' is always an asymptotic ideal." Dreams of the past, Nature 423 (6939): 121, 8 May 2003

tumor microenvironment (TME):  Consists of cells, soluble factors, signaling molecules, extracellular matrix, and mechanical cues that can promote neoplastic transformation, support tumor growth and invasion, protect the tumor from host immunity, foster therapeutic resistance, and provide niches for dormant metastases to thrive. An American Association for Cancer Research (AACR) special conference held on November 3–6, 2011, addressed five emerging concepts in our understanding of the TME: its dynamic evolution, how it is educated by tumor cells, pathways of communication between stromal and tumor cells, immunomodulatory roles of the lymphatic system, and contribution of the intestinal microbiota.    Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy Melody A. Swartz 1, Noriho Iida 2, Edward W. Roberts 3Sabina Sangaletti 4, Melissa H. Wong 5, Fiona E. Yull6, Lisa M. Coussens 5 , and  Yves A. DeClerck 7 Cancer Res May 15, 2012 72; 2473 Published OnlineFirst March 13, 2012; doi: 10.1158/0008-5472.CAN-12- 0122

tumoroid: Multicellular cancer “oids” (tumoroids, spheroids, organoids) provide models of intermediate complexity between standard two-dimensional culture systems and tumors in vivo. “Oids” exhibit physiologically relevant cell-cell and cell-matrix interactions, gene expression and signaling pathway profiles, heterogeneity and structural complexity that reflect in vivo tumors. When cultured properly, tumoroids form with relative ease and demonstrate the effectiveness, reproducibility, and robustness of this in vitro model system.  World Pharmaceutical Congress 2018 June 19-20, Boston MA

An aggregate of cancer cells formed in vitro  Wiktionary

uncertainty: The condition in which reasonable knowledge regarding risks, benefits, or the future is not available. MeSH 2003

The shift to a post- Mendelian view of genetics (with variable penetrance and eventually, insights into polygenic diseases) and genomics seems likely to result in more uncertainty, not less, at least for some time.

venture philanthropy

As noted in the OECD report, there’s no one definition or model for “venture philanthropy”—nor is one needed, because it’s “more of a blanket term, an expression of a more purpose-, results- and responsibility-driven worldview” many foundations now embrace. The report did find an “overlapping set of characteristics” that many venture philanthropy efforts share, although not all occur in every case: Strategic framing which coordinates targeted resources (grants and/or investments), so that collectively they create systemic change; Scales of intervention that address systems and sectors, rather than individual organizations or projects; Sector focuses that tend to be cross-sectoral, engaging civil society, markets, and/or governments as needed; Funding mechanisms that blend grants and investments, as appropriate to the theory of change; Engagement styles that are more hands-on, using extended interactions with and sometimes between grantees; Engagement periods that reflect the goal of systems changes, often five to ten years rather than one to two years.; Culture and capabilities that are focused on innovation and experimentation; Monitoring and evaluation that allows quick adaptation and focuses on outcomes and impacts.  Wait—What is Venture Philanthropy, Again?   EILEEN CUNNIFFE | March 12, 2014  
Venture Philanthropy: The New Model

Some patient advocacy groups are investing in companies working on therapeutics in their areas of interest, and may also help recruit patients for clinical trials. 

virtual molecules: It has also become clear that even the most efficient combinatorial chemistry approaches can generate only a minute fraction of the 1 x 1040 virtual drug molecules that could potetially be synthesized.  J. Patrick Walters Virtual Chemical Libraries, 2018 

FDA, Glossary Drugs@FDA,  2012,
Glick, David M., Glossary of Biochemistry and Molecular Biology. 2014. 
IUPAC  International Union of Pure and Applied Chemistry, Glossary of Terms used in Bioinorganic Chemistry, Recommendations, 1997. 450+ definitions.
King, Robert C. and William D. Stansfield, Dictionary of Genetics, Oxford University Press, 8th edition, 2012
MeSH Medical Subject Headings, (PubMed Browser) National Library of Medicine, Revised annually.  250,000 entry terms, 19,000 main headings. 
ORD Office of Rare Diseases NIH Medical & Science Glossaries  Rare diseases
Pelikan, Edward, Glossary of terms and symbols used in pharmacology, Boston University Medical School, US, 1993- 1998, about 300 definitions.
Schlindwein Birgid, Hypermedia Glossary of Genetic Terms, 2006. 670 definitions. 

How to look for other unfamiliar  terms

 IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

Contact | Privacy Statement | Alphabetical Glossary List | Tips & glossary FAQs | Site Map