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Proteomics Glossary & taxonomy

Evolving Terminology for Emerging Technologies
 Suggestions? Revisions? Comments? Questions? 
 Mary Chitty MSLS
mchitty@healthtech.com
Last revised September 12, 2019



PEGS: the essential protein engineering summit       PEGS: the essential protein engineering summit  May 2020 • Boston, MA Program | Conference programs include protein and antibody engineering, cancer immunotherapy, oncology, and emerging therapeutics

PEGS EuropePEGS Europe  2018 Nov 12-16  Lisbon Portugal . Conference programs include Engineering, Oncology, Analytical, Immunotherapy, Expression and Bispecifics.
 
  

PepTalk PepTalk  January 2020 • San Diego, CA Program | Conference programs include Protein Engineering and Development, Innovations in Discovery and Development, Antibody Therapeutics,  Formulation and Stability, Analytics & Impurities, Process Technologies & Purification, Biotherapeutic expression & production, Alternative expression & products.

Related Glossaries include Informatics
Protein Informatics
   AlgorithmsBioinformatics  Drug discovery informatics 
Technologies:  Protein Technologies  Chromatography & electrophoresis,  Mass spectrometryNMR & x-ray crystallography
Biology: Expression    Functional genomics  
 ProteinsProtein Structure  Proteomics categories
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bait: The basic format of the yeast-two hybrid system involves the creation of two hybrid molecules, one in which the "bait" protein is fused with a transcription factor, and one in which the "prey" protein is fused with a related transcription factor. If the bait and prey proteins indeed interact then the two factors fused to these two proteins are also brought into proximity with each other. As a result a specific signal is produced, indicating an interaction has taken place.

cellular proteome: All of the proteins expressed in a cell. Google = about 948 Oct. 25, 2006

complete proteome: Protein which is part of a proteome. A proteome is the set of protein sequences that can be derived by translation of all protein coding genes of a completely sequenced genome, including alternative products such as splice variants for those species in which these may occur. Proteomes may include protein sequences from both the reviewed (UniProtKB /Swiss-Prot) and unreviewed (UniProtKB/TrEMBL) sections of the UniProt Knowledgebase. Note that some proportion of the predicted protein sequences of a given proteome may require further review or correction. The precise proportion depends on the relative distributions of protein sequences between the two sections of UniProtKB and the quality of the underlying genome sequence and gene predictions. https://www.uniprot.org/keywords/KW-0181

dissociator assays: A collective term for yeast- one hybrid, yeast- two hybrid or yeast- three hybrid assays.  Google = about 25 Oct. 25, 2006

homointeraction: A lot of proteins interact with themselves. [Dr. Jong Paik, Bioinformatics/ Proteomics, Dunn Human Nutrition Unit, Medical Research Council,  UK, 2001] http://www.mrc-dunn.cam.ac.uk/research/bioinformatics_proteomics.html

Human Proteome Organisation HUPO: The reason for creating HUPO is to assist in increasing the awareness of this discipline of science across society, particularly with regard to the Human Proteome Project and to engender a broader understanding of the importance of proteomics and the opportunities it offers in the diagnosis, prognosis and therapy of disease. As a global body it will also have the objective of fostering international cooperation across the proteomics community and of promoting scientific research in an on- going manner around the world.. HUPO Human Proteome Organisation  http://www.hupo.org/

Human Proteome Initiative now Chordata Protein Annotation Program  http://www.uniprot. org/program/Chordata  one of the current priorities of the Chordata protein annotation program is to improve the quality of human sequences provided. To this aim, we are updating sequences which show discrepancies with those predicted from the genome sequence. Dubious isoforms, sequences based on experimental artefacts and protein products derived from erroneous gene model predictions are also revisited.

NHLBI Proteomics Core: provides access to mass spectrometry and gel-based proteomics for identification and quantitation of proteins and their post-translational modifications (PTM). https://www.nhlbi.nih.gov/science/proteomics-core

perturbagens: A substance (typically a peptide) designed to disrupt intracellular processes, providing information about the operation of pathways and networks within a cell. Wiktionary https://en.wiktionary.org/wiki/perturbagen

Used in physics to determine the effects of a number of variables upon a system.

pharmacoproteomics:   Pharmacogenomics Google = about 195 Sept. 18, 2002, about 488 July 14, 2004; about 12,200 Oct. 25, 2006

plasma proteome:
Comprehensive, systematic characterization of the plasma proteome in healthy and diseased states greatly facilitates the development of biosignatures for early disease detection, clinical diagnosis, and therapy. However, blood plasma is the most complex human-derived proteome containing other tissue proteome subsets as well as a wide dynamic range of protein concentrations. 

post-translational modifications: Proteins once synthesized on the ribosomes, are subject to a multitude of modification steps. They are cleaved (thus eliminating signal sequences, transit or pro- peptides and initiator methionines); many simple chemical groups can be attached to them … as well as some more complex molecules, such as sugars and lipes. Finally they can be internally or externally cross- linked. More than a hundred different types of post- translational modifications are currently known (Aug. 1999) and many more are yet to be discovered. The complexity due to all these modifications is compounded by the high level of diversity that alternative splicing can produce at the level of sequence. Thus the number of different protein molecules expressed by the human genome is probably closer to a million than to the hundred thousand generally considered by genome scientists. The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 Amos Bairoch* Rolf Apweiler  Nucleic Acids Research 28 (1): 45-48  http://nar.oxfordjournals.org/content/28/1/45.full?ref=klasshop.com  

Post-translational modification is a point of concern in the development of strategies for proteomics. Because these modifications cannot be inferred directly from gene sequence, they generally can only be characterized directly. This raises issues about sequence coverage and stoichiometry of modifications that are not presented by proteomics problems focused on protein identification. In particular, the complexity and diversity of glycosylation events significantly complicates the linkage between genetic sequence and mature, active proteins. Because glycosylation is mediated by a wide range of factors, discovery- based analytical tools that can survey the complexities of glycosylation on a system-wide basis may have significant biological impact. NCRR National Center for Research Resources, NIH, Integrated Biomedical Technology Research Resources for Proteomics and Glycomics,  RELEASE DATE: July 22, 2002 PA NUMBER: PA-02-132 http://grants.nih.gov/grants/guide/pa-files/PA-02-132.html 
Narrower terms: biotinylation, glycosylation, pegylation, phosphorylation, polyadenylation, prenylation, protein isoprenylation; Related terms: post- translational protein processing, proteolytic processing, ubiquitination; In silico & molecular modeling: post- translational modification prediction

post-translational protein processing: Any of various enzymically catalyzed post- translational modifications of peptides or proteins in the cell of origin. These modifications include carboxylation, hydroxylation, acetylation, glycosylation, methylation, phosphorylation, oxidation- reduction, degradation and lysis, peptide bond formation, and changes in molecular weight and electrophoretic motility. MeSH, 1983  Related terms: post- translational modifications; 

protein complexes:   http://en.wikipedia.org/wiki/Protein_complex    Related terms: complexome: -Omes & -omics; Metabolic engineering

protein expression: Is variable, not all encoded proteins are expressed at all times. More ... Expression  Bioprocessing 

protein-RNA interactions: The yeast three-hybrid system has become a useful tool in analyzing RNA–protein interactions. HOOK B, BERNSTEIN D, ZHANG B, WICKENS M. RNA–protein interactions in the yeast three-hybrid system: Affinity, sensitivity, and enhanced library screening. RNA. 2005;11(2):227-233. doi:10.1261/rna.7202705. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370711/ 

Involved in gene expression and protein synthesis Related terms: interaction proteomics; Omes & omics  riboproteomics; Cell biology  ribosome,  

proteome:
The scope note  for the Journal of Proteome Research (Jan.2002) states that "primary topics will include: New approaches to sample preparation, including 2- D gels and chromatographic techniques, Advancements in high- throughput protein identification and analysis, Array- based measurements, Structural genomics data related to protein function, Research on quantitative and structural analysis of proteins and their post- translational modifications, Metabolic and signal pathway analysis, including metabolomics and peptidomics, Protein- protein, protein- DNA, and protein- small molecule interactions, Computational approaches to predict protein function, Use of Bioinformatics/ Cheminformatics to mine and analyze data, New tools in proteomic analysis, Studies on proteomics with an impact on the understanding of disease, diagnosis and medicine. Scope note, Journal of Proteome Research, American Chemical Society http://pubs.acs.org/journals/jprobs/

Comprehensive quantitative data on the proteins of an organism under a variety of conditions (ideally including post synthetic modifications and interactions with other molecules). To achieve this, purification each protein (including modified versions and interacting antibodies) will be an important related project  George Church Lab, Harvard- Lipper Center for Computational Genomics, 2001 http://arep.med.harvard.edu/

The concept of the proteome is fundamentally different to that of the genome: while the genome is virtually static and can be well defined for an organism, the proteome continually changes in response to external and internal events. Marc Wilkins and Denis Hockstrasser "Thinking Big Proteome Studies in a Post- Genome Era" ABRF News Dec 1996 http://www.abrf.org/ABRFNews/1996/December1996/Proteome.html

Marc Wilkins is credited with coining the word in 1994 at the Conference on Genome and Protein Maps in Siena, Italy. PROTEin complement expressed by a genOME. Wilkins et al "Progress with gene product mapping of the Mollicutes" Electrophoresis 16:1090-1094, July 1995

The dynamic nature of the proteome calls for methods to monitor, for any organism, the entire proteome's conditional state accurately and sensitively from thousands of samples. This will require greater completeness, resolution, and sensitivity than has been possible in the past using conventional imaging and gel-based technologies. Also, new tools characterizing these complexes must be developed to bridge the current size and resolution gap between single proteins suitable for high-resolution X-ray crystallographic study and the very large protein assemblies and cellular ultrastructures amenable to electron microscopy.

Wikipedia http://en.wikipedia.org/wiki/Proteome 
Broader terms: Genomics  genome;  -Omes & -omics  ORFeome Related terms: -Omes & -omics translatome.  See translatome
for a discussion of the ambiguities in competing definitions of proteome.

proteomics:  The most useful definition of proteomics is likely to be the broadest: proteomics represents the effort to establish the identities, quantities, structures and biochemical and cellular functions of all proteins in an organism, organ, or organelle, and how these properties vary in space, time and physiological state. .. A much broader field than would be apparent from early efforts, which have focused on cataloging levels of protein expression.  Ideally it should encompass efforts to obtain complete functional descriptions for the gene products in a cell or organism.   Defining the Mandate of Proteomics in the Post- Genomics Era, National Academy of Sciences, 2002 http://www.nap.edu/books/NI000479/html/R1.html

The systematic study of the complete complement of proteins (PROTEOME) of organisms.  MeSH 2003

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

At present, the aggregate of activities called proteomics has three distinct technical subsets: protein profiling, protein- protein interaction and structural biology. ... [producing] voluminous amounts of data ... substantial attention is now being applied to annotation methods by which the resulting information, e.g., source protein, types of  modifications, subcellular organelle, cell expression profiles, known protein interaction, protein domain organization, atom- by- atom structural coordinates, etc. can be archived in a manner amenable by computer query and in silico cross references. Robert G. Urban, ZYCOS, Inc. "Proteomics: Making sense of the census" Current Drugs 5, Aug. 2001 http://www.current-drugs.com/CDD/CDD/CDDContents-August.htm

The use of quantitative protein- level measurements of gene expression to characterize biological processes (e.g. disease processes and drug effects) and decipher the mechanisms of gene expression control. As such, proteomics focuses on the dynamic description of gene regulation and, by doing  so, offers something much more powerful than a protein equivalent of DNA databases: the concept of molecular recognition as a systematic science.  For this reason, proteomics emphasizes quantitation and the assembly of large bodies of experimental observations in numerical databases N. Leigh Anderson, Norman G. Anderson "Proteome and proteomics; New technologies, new concepts, and new words" Electrophoresis 19 (11): 1853- 1861 August 1998

Industrial scale analysis of many proteins and their interactions, over time, ultimately tying this into physiological processes and biological pathways and networks. 

The earliest PubMed reference I've found to proteomics is P James' "Protein identification in the post- genome era: the rapid rise of proteomics" Quarterly Review of Biophysics 30(4): 279- 331, Nov. 1997. References to proteomic are just a little earlier (Ian Humphery- Smith and Walter Blackstock "Proteome analysis: genomics via the output rather than the input code" Journal of Protein Chemistry16(5): 537- 544, July 1997). Perhaps earlier references can be found in the chemical and/ or biophysics literature.

Variant spellings without (as far as I can tell) truly variant meanings seem to distinguish proteinomics and proteonics.  I would welcome any thoughts or comments on these words. Related term proteonomics  (Or is this just another variant spelling?) 

Wikipedia http://en.wikipedia.org/wiki/Proteomics 

Narrower terms: Proteomics categories applied proteomics,  bottom-up proteomics,   computational proteomics, differential,  functional proteomics,  location proteomics, ,  microproteomics, molecular proteomics, phosphoproteomics,  physiological proteomics, predictive proteomics, quantitative proteomics  quantitative proteomics, regulatory proteome, , reverse proteomics, , shotgun  proteomics, structural proteomics, subproteomics, , targeted, proteomics,  tissue proteomics, top down proteomics, toponomics

reverse-two hybrid: A variation of the yeast two hybrid system, in which protein- protein interactions increase the transcription of a toxic counterselectable marker, resulting in growth inhibition. The availability of a counterselectable marker significantly extends the possibilities of the two- hybrid system. Most importantly, dissociation of  protein- protein interactions can be selected for, and thus protein- protein interactions can be characterized and manipulated genetically. [Marc Vidal et al. "The reverse two- hybrid system and several of its applications "Yeast Genetics and Molecular Biology, Madison, WI August 1996] http://genome-www.stanford.edu/Saccharomyces/yeast96/f3041.html  

subproteomes: The separation of a complex mixture of proteins is often insufficient and many protein mixtures are dominated by a few major proteins. This makes the detection of many low abundance proteins difficult or even impossible. Therefore, covering a proteome as complete as possible often requires its separation into several subproteomes.  These "functional proteomics" approaches are especially useful when looking for answers to well defined biological questions. Affinity purification of proteins, separation of organelles or multiprotein complexes that take part in certain cellular functions are good examples of these approaches. Satu, Lehesranta, Introduction to Proteomics, Dept. Biochemistry, Univ. of Kuopio, Finland, 2001

Proteins found in a specific tissue, cell type or body fluid (may incorporate a temporal aspect as well.  

targeted proteomics: The goal of a targeted proteomics experiment is to monitor a select few proteins of interest with high sensitivity, reproducibility and quantitative accuracy.  Mass spectrometry–based targeted proteomics, Allison Doerr, Nature Methods 10,23 (2013) doi:10.1038/nmeth.2286 Published online 27 dec 2013 http://www.nature.com/nmeth/ journal/v10/n1/full/nmeth. 2286.html

two hybrid system techniques: Screening techniques used to identify genes encoding interacting proteins. Variations are used to evaluate complex interplay between proteins and other molecules. MeSH, 2000  Related term: yeast two hybrid

yeast one hybrid: A variant of the  yeast two- hybrid system, which identifies DNA- binding proteins from cDNA libraries or known gene sequences. Related term:  protein- DNA interactions

yeast three hybrid: The three-hybrid system enables the detection of RNA- protein interactions in yeast using simple phenotypic assays. It was developed in collaboration with Stan Fields laboratory (University of Washington- Seattle). Original publication of the method D. SenGupta, B. Zhang, B. Kraemer, P. Prochart, S. Fields and M. Wickens. 1996. A three- hybrid system for detecting RNA- protein interactions. Proc. Natl. Acad. Sci. 93, 8496- 8501 http://www.biochem.wisc.edu/wickens/3H/3HybrdSys_SenGupta.pdf   Marvin Wickens, Dept. of  Biochemistry,. Univ. of Wisconsin https://biochem.wisc.edu/labs/wickens/yeast-three-hybrid-system-wickens-lab

Modification of yeast two hybrid system. The third hybrid may be a first one with an RNA or with a small molecule that is a cell permeable chemical inducer of dimerization.   Related term  protein- RNA interactions.

yeast two hybrid: An approach to studying protein- protein interactions. The basic format involves the creation of two hybrid molecules, one in which a "bait" protein is fused with a transcription factor, and one in which a "prey" protein is fused with a related transcription factor. If the bait and prey proteins indeed interact, then the two factors fused to these two proteins are also brought into proximity with each other. As a result, a specific signal is produced, indicating an interaction has taken place. 

A system first developed in 1989 (by Stan Fields and colleagues) to identify proteins (and their genes) that interact with known proteins.   Related terms: dissociator assays, reverse two hybrid, two hybrid system techniques, bait, prey

Proteomics resources
National Academy of Sciences, Defining the Mandate of Proteomics in the Post- Genomics Era,  2002 http://www.nap.edu/books/NI000479/html/R1.html
Nature Proteomics, Mar 2003 http://www.nature.com/nature/insights/6928.html 
Nature Reviews Proteomics, 2005   http://www.nature.com/reviews/focus/proteomics/index.html 
UNI-PROT KnowledgeBase keywords,  Swiss Institute of Bioinformatics, Geneva Switzerland, European Bioinformatics Institute, Hinxton, UK, PIR Protein Information Resource, 2017 http://beta.uniprot.org/keywords/ 

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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