Proteomics: An Overview

WHAT DOES IT MEAN?The application of genomics has established a firm foundation for research into both human health and disease, and the development of proteomics was the next logical step, but what exactly is proteomics?The term proteomics was first coined in 1995 from a combination of ''protein'' and ''genomics,'' but it was far earlier in 1979 that the concept to fully characterize the human proteome was first proposed by Norman G. Anderson and N. Leigh Anderson in a submission entitled the ''Human Proteins Index Project.'' 1 At that time it was hoped that, by using the newly developed technique of 2-dimensional gel electrophoresis (2D-PAGE), the genome would be unlocked through the proteins identified.Since then, like most things in the field of science, the understanding of proteomics has evolved.The term proteomics now encompasses the concept of completeness, the idea that all proteins should be identified and studied.Already 1 study that fully incorporates this concept of completeness is that by the Protein Structure Initiative of the National Institutes of General Medical Sciences (NIGMS).Its aim is to generate a comprehensive database of all protein structures found in nature (http://www.nigms.nih.gov).This aim, however, is beyond the scope and ability of all but the largest scientific consortiums, and so the logical progression from generic protein identification for most researchers is the analysis of those proteins present within a chosen tissue, or cell population, with the aim of developing pattern recognition of the proteins expressed.Any differences observed in protein expression between different tissues can be examined, and groups or individual proteins examined in greater detail.Such a technique could allow for the characterization of specific protein markers of inflammation that are differentially expressed between inflamed and noninflamed intestinal tissue, and perhaps the identification of cellular markers of malignant change.Because of the huge number of proteins expressed in any 1 tissue, such wide-ranging profiling would primarily use high-throughput technologies to characterize the changes.These findings, however, are merely a snap shot of the protein levels at a single moment in time, and determination of changes in protein expression and location over time would engender greater information.Whether researchers aim to compare a proteomic snapshot of health with diseased states or characterize the changes observed over time under specific environmental conditions, protein expression profiles can be mapped.As more tissues are studied under more conditions, more and more changes will be identified.As more is known, the complexity of the protein patterning will ever increase, and thus use of bioinformatics and the techniques of computational simulation and modeling are vital to amalgamate the information into a coherent larger picture.Despite the vastness of the above concept of proteomics, however, its functional definition is still limited.A more inclusive definition is still desirable, because the understanding of proteins needs to extend far beyond merely the identification of protein expression profiles.To this purpose, the definition of proteomics should be expanded to represent ''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, or physiological state.'' 2Because the structure and function of proteins are not fixed, but vary over time and are dependent on the tissue microenvironment, proteomics needs to come to grips with protein modification, protein variants, and protein isoforms.This unfortunately magnifies the task dramatically.The simplest scenario of the proteome assumes that only 1 protein is encoded from every gene locus, with an estimated 20 to 25,000 nonredundant proteins encoded by the human genome.Genetic diversity of proteins from separate individuals, however, is a factor that results in amino acid variability and, as it occurs in greater than 1% of the population, 3 would increase