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Functional genomics glossary & taxonomy

Evolving Terminology for Emerging Technologies
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Mary Chitty MSLS
Last revised January 09, 2020 

Functional assessment of every gene in the mammalian cell is an on-going challenge. Understanding, not only the function of each gene in isolation but the complexity of functional networks and control systems is of particular importance for discovery of novel and valid drug targets. Answering complex biological questions in this context necessitates high- throughput gene functional characterization using an array of genomic, proteomic and in silico- based tools and technologies.  

Related glossaries include  Metabolic engineering,   Phylogenomics Drug discovery & development    Proteomics  
Informatics Bioinformatics,    Drug discovery & development informatics    Genomic informatics    Protein informatics
Technologies Genomic technologies     PCR,      Genetic Manipulation & disruption,     Microarrays
Biology Cell biology,    Chemistry & biology     Expression     Gene Definitions,    SNPs & genetic variations   Nomenclature
, particularly of genes in humans and in Model & other Organisms is an increasing challenge as comparing completed genomes becomes increasingly possible.  -Omes & omics

age: The time period elapsed since an identifiable point in the life cycle of an organism. (If a developmental stage is specified, the identifiable point would be the beginning of that stage. Otherwise the identifiable point must be specified such as planting).

A good illustration of the challenges inherent in cross species comparisons. 

biochemical function: My research is concerned with the three-dimensional structures of proteins and their biochemical functions. Gregory Petsko, Brandeis University, 2007

biological function: One key problem in this discussion involves the definition of "biological function".  Geneticists, cellular biologists, structural biologists, bioinformaticians, and biophysical chemists use this term to mean different things.  Some speakers used the word "function" to refer to the general biochemical activity of the gene produce (e.g. kinase activity), others referred to the cellular process in which the gene product is involved, while to others "function" meant an understanding of the details of the atomic mechanism of catalysis or recognition.  Still others referred to function in the genetic sense of a generalized phenotype.  This lack of consensus in defining what aspect of function one might learn about from an examination of protein structure prevented the group from reaching a consensus on the role that large scale structural genomics will have in the related area of functional genomics.  G. T. Montelione and S. Anderson, Report to the National Science Foundation:  Workshop on Structural Genomics - Understanding Proteins Universal to Life" Advanced Photon Light Source, Argonne Natl. Laboratories, Jan. 23 - 25, 1998 

biological function The Gene Ontology (GO) provides a framework and set of concepts for describing the functions of gene products from all organisms. It is specifically designed for supporting the computational representation of biological systems. A GO annotation is an association between a specific gene product and a GO concept, together making a statement pertinent to the function of that gene. However, the meaning of the term “function” is not as straightforward as it might seem, and has been discussed at length in both philosophical and biological circles. Here, I first review these discussions. I then present an explicit formulation of the biological model that underlies the GO and annotations, and discuss how this model relates to the broader debates on the meaning of biological function. The Gene Ontology and the Meaning of Biological Function, Paul D. Thomas  The Gene Ontology Handbook pp 15-24|, 2016

Related terms: biological process, Gene Ontology (GO)  Broader term: function

biological process: A biological objective to which the gene or gene product contributes. Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000

A biological process is accomplished via one or more ordered assemblies of molecular functions. Usually there is some temporal aspect to it, although a process event may be essentially instantaneous. It often involves transformation, in the sense that something goes into a process and something different comes out of it. ...  A biological process is not equivalent to a pathway. We are specifically not capturing or trying to represent any of the dynamics or dependencies that would be required to describe a pathway. [The semantic distinction between a biological process and a molecular function can, at times, be hard to draw, and GO takes a pragmatic, rather than dogmatic, approach: As a general rule a process must have >1 distinct steps.] Gene Ontology Consortium General Documentation, 2001

comparative genomics: "We believe that the problem of the genome- phenotype connection, which, in a sense, is the central theme of biology, can be solved only through an experimental program strategically planned on the basis of comparative- genomic results. Much of the biological research of the next few decades is likely to develop along these lines. E. Koonin et al "The Impact of Comparative Genomics on our Understanding of Evolution" Cell 101:573-576 June 9, 2000 

Insights can be biochemical, genetic, metabolic or physiological. The practice of uncovering the functions of human genes and other DNA regions by studying their parallels in nonhumans. 
Related terms: biological process, molecular function,  Gene Ontology Consortium; Cell biology cellular components; Maps genomic & genetic comparative genome mapping; Model & other organisms; Phylogenomics comparative proteomics, evolutionary genomics,  Narrower terms: comparative plant genomics, vertebrate comparative genomics
Background on Comparative Genomic Analysis, NHGRI, 2007  

deductive genomics:  deductive genomics, or large-scale forward genetics, bridges the gap between sequence and function by providing a function-driven in vivo screen of a highly orthologous mammalian model genome for medically relevant physiological functions and drug targets. This approach allows drug discovery to move beyond the focus on sequence-driven identification of new members of classical drug-able protein families towards the biology-driven identification of innovative targets and biological pathways. Deductive genomics: a functional approach to identify innovative drug targets in the post-genome era. Stumm G, Russ A, Nehls M., Am J Pharmacogenomics. 2(4): 263- 271, 2002 

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 

function as conceived by molecular biologists (in what could be called the “molecular biology paradigm”) refers to specific, coordinated activities that have the appearance of having been designed for a purpose. That apparent purpose is their function. The appearance of design derives from natural selection, so many biologists now favor the use of the term “biological program” to avoid connotations of intentional design. Following this convention, biological programs, when executed, perform a function; that is, they result in a particular, previously selected outcome or causal effect. Biological programs are nested modularly inside other, larger biological programs, so a protein can be said to have functions at multiple levels.  The Gene Ontology defines the “universe” of possible functions a gene might have, but it makes no claims about the function of any particular gene. Those claims are, instead, captured as “GO annotations.” A GO annotation is a statement about the function of a particular gene…The Gene Ontology (GO) considers three distinct aspects of how gene functions can be described: molecular function, cellular component, and biological process.   In this representation, a gene encodes a gene product, and that gene product carries out a molecular-level process or activity (molecular function) in a specific location relative to the cell (cellular component), and this molecular process contributes to a larger biological objective (biological process) comprised of multiple molecular-level processes.  The Gene Ontology and the Meaning of Biological Function, Paul D. Thomas  The Gene Ontology Handbook pp 15-24|, 2016

Narrower terms:  biological function, gene function; Proteomics protein function. Related terms: Gene Ontology TM Omes & omics functome, transcriptome

functional genome annotation: Functional annotation of the genome is primarily hampered by the lack of a unified transcript index. Current transcript information still largely consists of anonymous and highly redundant ESTs. The situation is further complicated by extensive splicing variation and elusive gene expression. To address these problems, the Ensembl consortium relies initially on computational prediction, followed by confirmation with EST/ protein alignments... We have found evidence for a large number of transcriptional units (65,000- 75,000) and performed initial annotation and classification. The effective study of transcription and protein function requires the compilation of all available evidence of transcription and protein homology. FA Wright et. al. A draft annotation and overview of the human genome, Genome Biology 2(7): 2001

functional genomics:  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 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. 


Related terms: biological process,  genome function,  molecular function, Metabolic profiling networks, pathways,  physiological genomics;  Phylogenomics comparative genomics, homology, phylogenomics,

functional genomics data: A useful way to tackle noise and complexity of functional genomics information is to average the data from many different genes into broad 'omic categories (Jansen & Gerstein 2000. For instance, instead of looking at how the level of expression of an individual gene changes over a time- course, we can average all the genes in a functional category (e.g. glycolysis) together. This gives a more robust answer about the degree to which a functional system changes over the time- course. Dov Greenbaum, Mark Gerstein et. al. "Interrelating Different Types of  Genomic Data" Dept. of Biochemistry and Molecular Biology, Yale Univ. 2001 Related terms: Omes & omics

functional genomics technologies: Conditional or tissue- specific gene expression in animal models is a major area of interest. Other increasingly popular methods of downregulating gene expression, in order to study function, include antisense, ribozyme, and zinc finger protein (ZFP) approaches. In addition, a limited number of companies have developed chemical- genetics methods. Include gene disruption, gene manipulation, gene shuffling, gene targeting, gene trapping, knockdowns, knockins, knockouts, mutagenesis, phage display, positional cloning, Post Translational Gene Silencing PTGS; RNA interference RNAi. 
Related terms chemical genetics, chemical genomics

functional homology: Sequence homology does not necessarily indicate functional homology. A number of labs are working with yeast and other non-human organisms to try to determine what the relationship between sequence and function might be, if there is any. 

functional profiling:  Linking genes and proteins to disease. 

gene function: The lack of a common language for gene functions is … proving to be a serious problem. E Pennisi "Seeking common language in a Tower of Babel" Science 286 (5439): 449 Oct. 15 1999

The nature of gene function was substantially specified by George W. Beadle and Edward Tatum [19] and Adrian M. Srb and Norman H. Horowitz [20] when they showed, using Neurospora crassa (Ascomycetes) as their experimental organism, that genes control the synthesis of enzymes, and in particular that each individual gene is responsible for the synthesis of one single enzyme. This one gene - one enzyme hypothesis was the culmination of the classical view of the gene. ... The classical concept of the gene started to break down as soon as it had been completely formulated.  Petter Portin in "The Origin, Development and Present Status of the Concept of the Gene: A Short Historical Account of the Discoveries" Univ. of Turku, Finland, Current Genomics, 2000  Related terms: biological function, function, genome function, molecular function; protein function Proteomics

genome function: Efficient interpretation of the functions of human genes and other DNA sequences requires that resources and strategies be developed to enable large- scale investigations across whole genomes. A technically challenging first priority is to generate complete sets of full- length cDNA clones and sequences for human and model- organism genes. Other functional genomics goals include studies into gene expression and control, creation of mutations that cause loss or alteration of function in nonhuman organisms, and development of experimental and computational methods for protein analyses. [Oak Ridge National Lab, Human Genome Management Information Services, US]

genome integrity: Maintaining the integrity of genetic information is fundamental for the life of a cell and the survival of a species. Cells can encounter DNA damage as a consequence of normal cellular metabolism or as a result of exposure to chemical or physical agents.  Related term: DNA repair

hypomorph: Loss of function.  Related term: null mutation

interactions- molecular: Related terms: Biomolecules  biomolecular interactions; Omes & omics interactome; Proteomics protein- DNA interactions, protein- protein interactions, protein- RNA interactions; RNAi: RNA- RNA interactions

knockout mice: Model & other organisms  Knockout-mouse technology is considered an essential and standard technique in functional genomics and target validation. 

molecular function: The biochemical activity including specific binding to ligands or structures) of a gene product. This definition also applied to the capability that a gene product (or gene product complex) carries as a potential. It describes only what is done without specifying where or when the event actually occurs.  Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000

There is a potential for semantic confusion between a gene product and its molecular function, because very often these are described in exactly the same words. For example, "alcohol dehydrogenase" can describe what you can put in an Eppendorf tube (gene product) or it can describe the function of this stuff. There is, however, a formal difference -- a "product" has a (potentially) many- to- many relationship with a "molecular function."  Gene Ontology Consortium General Documentation, 2001  
Related terms: biological function, biological process, function, gene function, Gene OntologyTM; Cell biology cellular component Gene definitions gene product 

OBO Foundry Ontologies 

ortholog (orthologue): That relationship where sequence divergence follows speciation, that is, where the common ancestor of the two genes lines in the cenancestor of the taxa from which the two sequences were obtained … There is a tendency to wish that there could be only one ortholog in an organism. This is frequently not the case. Walter Fitch “Homology a personal view on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000  Narrower term: Phylogenomics super- orthologs

orthologous: Homologous sequences in different species that arose from a common ancestral gene during speciation; may or may not be responsible for a similar function. NCBI Bioinformatics

paralog (paralogue): That condition where sequence divergence follows gene duplication. Such genes might descend and diverge while existing side by side in the same lineage. Walter Fitch “Homology a personal view on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000  Narrower term: Phylogenomics ultra- paralogs

paralogous: Homologous sequences within a single species that arose by gene duplication. NCBI Bioinformatics Related term:  SNPs & Genetic variations duplication  

positional cloning: Involves using a genetic map to determine the location of a disease gene. Researchers use such maps to analyze genetic markers in extended families that include individuals affected by a heritable disease, and to pinpoint regions of the genome that are associated with the disease. They then use that information to isolate the DNA from the region, and to identify and sequence the disease gene and identify mutations. 

A process which, through gene mapping techniques, is able to locate a gene responsible for a disease when little or no information is known about the biochemical basis of the disease. [NHGRI] cloning requires a genetic map with a large number of markers (especially in the region of interest), and the use of physical mapping and DNA sequencing technologies to isolate and sequence the targeted gene. A disease gene is usually identified from among candidate genes in the region of interest by showing that affected individuals carry mutations within that gene. 

Positional cloning was incorrectly called "reverse genetics" early on. Reverse genetics in its purest definition refers to the analysis of gene function by assaying proteins expressed from gene variants. "[Positional cloning] is not "reverse" at all, but rather genetics in its purest form, unadulterated by any influences of biochemistry, cell biology or physiology." ( Francis S Collins "Positional cloning: Let’s not call it reverse anymore" Nature Genetics. 1: 3-6, 1992)The term "positional cloning" was coined by Francis Collins.  Related terms: functional cloning, positional candidate approach;  Genetic variations and SNPs candidate gene approach; Maps- genomic & genetic

similarity: The extent to which nucleotide or protein sequences are related. Similarity between two sequences can be expressed as percent sequence identity and/or percent positive substitutions. BLAST Glossary   Related term: homology

siRNA Small interfering RNA: May be useful in assessing gene function Related terms: RNA  RNAi, Post-Transcriptional Gene Silencing PTGS

xenology (xenologous): That conditional (horizontal transfer) where the history of the gene involves an interspecies transfer of genetic material. It does not include transfer between organelles and the nucleus.  It is the only form of homology in which the history has an episode where the descent is not from parent to offspring but, rather, from one organism to another … Gogarten has proposed a special term, synology, for those xenologs that arise, not by the transfer of a gene between two species, but by a hybridization of two species.  Walter Fitch “Homology a personal view on some of the problems” Trends in Genetics 16 (5): 227-231 May 2000

ArrayExpress, European Bioinformatics Institute  Functional genomics data repository

How to look for other unfamiliar  terms

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

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