“Systems biology…is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different….It means changing our philosophy, in the full sense of the term” (Denis Noble).
From Wikipedia, the free encyclopedia
For the journal Proteomics, see Proteomics (journal).
Proteomics is the large-scale study of proteins, particularly their structuresand functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells.
The term proteomics was first coined in 1997 to make an analogy with genomics, the study of the genome. The word proteome is a blend of protein and genome, and was coined by Marc Wilkins in 1994 while working on the concept as a PhD student.
The proteome is the entire set of proteins, produced or modified by an organism or system. This varies with time and distinct requirements, or stresses, that a cell or organism undergoes.
Proteomics is an interdisciplinary domain formed on the basis of the research and development of the Human Genome Project; it is also emerging scientific research and exploration of proteomes from the overall level of intracellular protein composition, structure, and its own unique activity patterns. It is an important component of functional genomics.
While proteomics generally refers to the large-scale experimental analysis of proteins, it is often specifically used for protein purification and mass spectrometry.
1 Complexity of the problem
1.1 Post-translational modifications
1.1.3 Additional modifications
1.2 Distinct proteins are made under distinct settings
2 Limitations of genomics and proteomics studies
3 Methods of studying proteins
3.1 Protein Detection with Immunoassays
3.2 Identifying proteins that are post-translationally modified
3.3 Determining the existence of proteins in complex mixtures
3.4 Computational methods in studying protein biomarkers
4 Establishing protein–protein interactions
5 Practical applications of proteomics
5.3 Current research methodologies
6 Bioinformatics for Proteomics
7 Structural proteomics
8 Expression proteomics
9 Interaction proteomics
10 Proteomics and System Biology
11 Current Proteomic Technologies
11.1 Mass Spectrometry and Protein Profiling
11.2 Protein Chips
11.3 Reverse Phased Protein Microarrays
12 Emerging trends in Proteomics
12.1 Human Plasma Proteome
13 See also
13.1 Protein databases
13.2 Research centers
16 External links
Complexity of the problem
After genomics and transcriptomics, proteomics is the next step in the study of biological systems. It is more complicated than genomics because an organism’s genome is more or less constant, whereas the proteome differs from cell to cell and from time to time. Distinct genes are expressed in different cell types, which means that even the basic set of proteins that are produced in a cell needs to be identified.
In the past this phenomenon was done by mRNA analysis, but it was found not to correlate with protein content. It is now known that mRNA is not always translated into protein, and the amount of protein produced for a given amount of mRNA depends on the gene it is transcribed from and on the current physiological state of the cell. Proteomics confirms the presence of the protein and provides a direct measure of the quantity present.
Not only does the translation from mRNA cause differences, but many proteins are also subjected to a wide variety of chemical modifications after translation. Many of these post-translational modifications are critical to the protein’s function.
One such modification is phosphorylation, which happens to many enzymes and structural proteins in the process of cell signaling. The addition of a phosphate to particular amino acids—most commonly serine and threonine mediated by serine/threonine kinases, or more rarely tyrosine mediated by tyrosine kinases—causes a protein to become a target for binding or interacting with a distinct set of other proteins that recognize the phosphorylated domain.
Because protein phosphorylation is one of the most-studied protein modifications, many “proteomic” efforts are geared to determining the set of phosphorylated proteins in a particular cell or tissue-type under particular circumstances. This alerts the scientist to the signaling pathways that may be active in that instance.
Ubiquitin is a small protein that can be affixed to certain protein substrates by enzymes called E3 ubiquitin ligases. Determining which proteins are poly-ubiquitinated helps understand how protein pathways are regulated. This is, therefore, an additional legitimate “proteomic” study. Similarly, once a researcher determines which substrates are ubiquitinated by each ligase, determining the set of ligases expressed in a particular cell type is helpful.
Listing all the protein modifications that might be studied in a “proteomics” project would require a discussion of most of biochemistry. Therefore, a short list illustrates the complexity of the problem. In addition to phosphorylation and ubiquitination, proteins can be subjected to (among others) methylation, acetylation, glycosylation, oxidation and nitrosylation. Some proteins undergo all these modifications, often in time-dependent combinations. This illustrates the potential complexity of studying protein structure and function.
Practical applications of proteomics
One major development to come from the study of human genes and proteins has been the identification of potential new drugs for the treatment of disease. This relies on genome and proteome information to identify proteins associated with a disease, which computer software can then use as targets for new drugs. For example, if a certain protein is implicated in a disease, its 3D structure provides the information to design drugs to interfere with the action of the protein. A molecule that fits the active site of an enzyme, but cannot be released by the enzyme, inactivates the enzyme. This is the basis of new drug-discovery tools, which aim to find new drugs to inactivate proteins involved in disease. As genetic differences among individuals are found, researchers expect to use these techniques to develop personalized drugs that are more effective for the individual.
Proteomics is also used to reveal complex plant-insect interactions that help identify candidate genes involved in the defensive response of plants to herbivory.[
Proteomics and System Biology
Proteomics has recently come into the act as a promising force to transform biology and medicine. It is becoming increasingly apparent that changes in mRNA expression correlate poorly with protein expression changes. Proteins changes enormously in patterns of expressions across developmental and physiological responses. Proteins also face changes on the act of environmental perturbations. Proteins are the actual effectors driving cell behavior. The field of proteomics strives to characterize protein structure and function, protein-protein,protein-nucleic acid, protein-lipid, and enzyme-substrate interactions, protein processing and folding, protein activation, cellular and sub-cellular localization, protein turnover and synthesis rates, and even promoter usage. Integrating proteomic data with information such as gene, mRNA and metabolic profiles helps in better understanding of how the system works.
Activity based proteomics
List of biological databases
List of omics topics in biology
Yeast two-hybrid system
Human Protein Atlas
Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)
Human Protein Reference Database
Model Organism Protein Expression Database (MOPED)
National Center for Biotechnology Information (NCBI)
Protein Data Bank (PDB)
Protein Information Resource (PIR)
Proteomics Identifications Database (PRIDE)
Proteopedia The collaborative, 3D encyclopedia of proteins and other molecules
European Bioinformatics Institute
Netherlands Proteomics Centre (NPC)
Proteomics Research Resource for Integrative Biology (NIH)
Global map of proteomics labs
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Twyman RM (2004). Principles Of Proteomics (Advanced Text Series). Oxford, UK: BIOS Scientific Publishers. ISBN 1-85996-273-4. (covers almost all branches of proteomics)
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Proteomics on the Open Directory Project
Look up proteomics in Wiktionary, the free dictionary.
Wikibooks has more on the topic of: Proteomics
At Wikiversity you can learn more and teach others aboutProteomics at:
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From Wikipedia, the free encyclopedia
Personalized medicine or PM is a medical model that proposes the customization of healthcare – with medical decisions, practices, and/or products being tailored to the individual patient. In this model, diagnostic testing is essential for selecting appropriate therapies; terms used to describe these tests include “”companion diagnostics”, “theranostics” (a portmanteau of therapeutics and diagnostics), and “therapygenetics”. The use of genetic information has played a major role in certain aspects of personalized medicine, and the term was even first coined in the context of genetics (though it has since broadened to encompass all sorts of personalization measures). To distinguish from the sense in which medicine has always been inherently “personal” to each patient, PM commonly denotes the use of some kind of technology or discovery enabling a level of personalization not previously feasible or practical.
3.1 Cancer management
4 Psychiatry and psychological therapy
5 See also
7 Further reading
8 External links
Traditional clinical diagnosis and management focuses on the individual patient’s clinical signs and symptoms, medical and family history, and data from laboratory and imaging evaluation to diagnose and treat illnesses. This is often a reactive approach to treatment, i.e., treatment/medication starts after the signs and symptoms appear.
Advances in medical genetics and human genetics have enabled a more detailed understanding of the impact of genetics in disease. Large collaborative research projects (for example, the Human genome project) have laid the groundwork for the understanding of the roles of genes in normal human development and physiology, revealed single nucleotide polymorphisms (SNPs) that account for some of the genetic variability between individuals, and made possible the use of genome-wide association studies (GWAS) to examine genetic variation and risk for many common diseases.
Historically, the pharmaceutical industry has developed medications based on empiric observations and more recently, known disease mechanisms. For example, antibiotics were based on the observation that microbes produce substances that inhibit other species. Agents that lower blood pressure have typically been designed to act on certain pathways involved in hypertension(such as renal salt and water absorption, vascular contractility, and cardiac output). Medications for high cholesterol target the absorption, metabolism, and generation of cholesterol. Treatments for diabetes are aimed at improving insulin release from the pancreas and sensitivity of the muscle and fat tissues to insulin action. Thus, medications are developed based on mechanisms of disease that have been extensively studied over the past century. It is hoped that recent advancements in the genetic etiologies of common diseases will improve pharmaceutical development.
Since the late 1990s, the advent of research using biobanks has brought advances in molecular biology, proteomics, metabolomicanalysis, genetic testing, and molecular medicine. Another significant development has been the notion of companion diagnostics, whereby molecular assays that measure levels of proteins, genes, or specific mutations are used to provide a specific therapy for an individual’s condition – by stratifying disease status, selecting the proper medication, and tailoring dosages to that patient’s specific needs. Additionally, such methods might be used to assess a patient’s risk factor for a number of conditions and tailor individualpreventative treatments.
Pharmacogenetics (also termed pharmacogenomics) is the field of study that examines the impact of genetic variation and responses to therapeutic interventions by biomarker (medicine). This approach is aimed at tailoring drug therapy at a dosage that is most appropriate for an individual patient, with the potential benefits of increasing the efficacy and safety of medications. Other benefits include reduced time, cost, and failure rates of clinical trials in the production of new drugs by using precise biomarkers. Gene-centered research may also speed the development of novel therapeutics.
The field of proteomics, or the comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by thehuman genome, may eventually have a significant impact on medicine. This is because while the DNA genome is the information archive, it is the proteins that do the work of the cell: the functional aspects of the cell are controlled by and through proteins, not genes.
It has also been demonstrated that pre-dose metabolic profiles from urine can be used to predict drug metabolism.Pharmacometabolomics refers to the direct measurement of metabolites in an individual’s bodily fluids, in order to predict or evaluate the metabolism of pharmaceutical compounds.
Some examples of personalized medicine include:
Genotyping for SNPs in genes involved in the action and metabolism of warfarin (Coumadin). This medication is used clinically as an anticoagulant but requires periodic monitoring and is associated with adverse side affects. Recently, genetic variants in the gene encoding Cytochrome P450 enzyme CYP2C9, which metabolizes warfarin, and the Vitamin K epoxide reductase gene (VKORC1), a target of coumarins, have led to commercially-available testing that enables more accurate dosing based on algorithms that take into account the age, gender, weight, and genotype of an individual.
Genotyping variants in genes encoding Cytochrome P450 enzymes (CYP2D6, CYP2C19, and CYP2C9), which metabolize neuroleptic medications, to improve drug response and reduce side-effects.
Oncology is a field of medicine with a long history of classifying tumor stages and subtypes based on anatomic and pathologic findings. This approach includes histological examination of tumor specimens from individual patients (such as HER2/NEU in breast cancer) to look for markers associated with prognosis and likely treatment responses. Thus, “personalized medicine” was in practice long before the term was coined. New molecular testing methods have enabled an extension of this approach to include testing for global gene, protein, and protein pathway activation expression profiles and/or somatic mutations in cancer cells from patients in order to better define the prognosis in these patients and to suggest treatment options that are most likely to succeed.
Examples of personalized cancer management include:
Companion diagnostics for targeted therapies.
Trastuzumab (trade names Herclon, Herceptin) is a monoclonal antibody drug that interferes with the HER2/neu receptor. Its main use is to treat certain breast cancers. This drug is only used if a patient’s cancer is tested for overexpression the HER2/neu receptor. Two of the most common tests used are the (Dako) HercepTest and Genentech’s Herceptin. Only Her2+ patients will be treated with Herceptin therapy (trastuzumab)
Tyrosine kinase inhibitors such as imatinib (marketed as Gleevec) have been developed to treat chronic myeloid leukemia(CML), in which the BCR-ABL fusion gene (the product of a reciprocal translocation between chromosome 9 and chromosome 22) is present in >95% of cases and produces hyperactivated abl-driven protein signaling. These medications specifically inhibit the Ableson tyrosine kinase (ABL) protein and are thus a prime example of “rational drug design” based on knowledge of disease pathophysiology.
Testing for disease-causing mutations in the BRCA1 and BRCA2 genes, which are implicated in hereditary breast–ovarian cancer syndromes. Discovery of a disease-causing mutation in a family can inform “at-risk” individuals as to whether they are at higher risk for cancer and may prompt individualized prophylactic therapy including mastectomy and removal of the ovaries. This testing involves complicated personal decisions and is undertaken in the context of detailed genetic counseling. More detailed molecular stratification of breast tumors may pave the way for future tailored treatments. These tests are part of the emerging field ofcancer genetics, which is a specialized field of medical genetics concerned with hereditary cancer risk.
Psychiatry and psychological therapy
Efforts are underway to apply the tools of personalized medicine to psychiatry and psychological therapy; these technologies are still under development as of 2013.
In 2012 Professor Thalia Eley and her research team coined the term “therapygenetics” refers to a branch of psychiatric genetic research looking at the relationship between specific genetic variants and differences in the level of success of psychological therapy. The field is parallel to pharmacogenetics, which explores the association between specific genetic variants and the efficacy of drug treatments. Therapygenetics work also relates to the differential susceptibility hypothesis  which proposes that individuals have a genetic predisposition to respond to a greater or lesser extent to their environment, be it positive or negative.
Whole genome sequencing
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