Technology - Proteomics

Molecular biologist's guide to proteomics

Graves, PR & Haystead, TAJ, 2002. Microbiol. Molec. Biol. Rev. 66(1):39-63

Abstract

The emergence of proteomics, the large-scale analysis of proteins, has been inspired by the realization that the final product of a gene is inherently more complex and closer to function than the gene itself. Shortfalls in the ability of bioinformatics to predict both the existence and function of genes have also illustrated the need for protein analysis. Moreover, only through the study of proteins can posttranslational modifications be determined, which can profoundly affect protein function. Proteomics has been enabled by the accumulation of both DNA and protein sequence databases, improvements in mass spectrometry, and the development of computer algorithms for database searching. In this review, we describe why proteomics is important, how it is conducted, and how it can be applied to complement other existing technologies. We conclude that currently, the most practical application of proteomics is the analysis of target proteins as opposed to entire proteomes. This type of proteomics, referred to as functional proteomics, is always driven by a specific biological question. In this way, protein identification and characterization has a meaningful outcome. We discuss some of the advantages of a functional proteomics approach and provide examples of how different methodologies can be utilized to address a wide variety of biological problems.

Journal Link | PMID

Comment

A very good introduction to proteomic approaches for both the novice and the experienced faculty due, in part, to it being published in 2002.  Thus, it does not make many of the assumptions of background common in more recent reviews.  Also, it is very well illustrated and documented for it time.  The diagrams are quite appropriate for self-learning by the novice and for use in medical school courses.

Viral Proteomics

Maxwell, KL & Frappier, L, 2007. Microbiol. Mol. Biol. Rev. 71(2):398-411

Abstract

Viruses have long been studied not only for their pathology and associated disease but also as model systems for molecular processes and as tools for identifying important cellular regulatory proteins and pathways. Recent advances in mass spectrometry methods coupled with the development of proteomic approaches have greatly facilitated the detection of virion components, protein interactions in infected cells, and virally induced changes in the cellular proteome, resulting in a more comprehensive understanding of viral infection. In addition, a rapidly increasing number of high-resolution structures for viral proteins have provided valuable information on the mechanism of action of these proteins as well as aided in the design and understanding of specific inhibitors that could be used in antiviral therapies. In this paper, we discuss proteomic studies conducted on all eukaryotic viruses and bacteriophages, covering virion composition, viral protein structures, virus-virus and virus-host protein interactions, and changes in the cellular proteome upon viral infection.

Journal Link | PMID

Comment

A very good, but shorter review of proteomic approaches and, thus, more dense than the earlier review by Graves & Haystead (above).  Although focused on viral systems it does a good job of illustrating general principles and the newer technological approaches.  The illustrations are very good.

Population proteomics: the concept, attributes, and potential for cancer biomarker research.

Nedelkov D et al., 2006. Mol Cell Proteomics 5(10):1811-8.

This review outlines the concept of population proteomics and its implication in the discovery and validation of cancer-specific protein modulations. Population proteomics is an applied subdiscipline of proteomics engaging in the investigation of human proteins across and within populations to define and better understand protein diversity. Population proteomics focuses on interrogation of specific proteins from large number of individuals, utilizing top-down, targeted affinity mass spectrometry approaches to probe protein modifications. Deglycosylation, sequence truncations, side-chain residue modifications, and other modifications have been reported for myriad of proteins, yet little is know about their incidence rate in the general population. Such information can be gathered via population proteomics and would greatly aid the biomarker discovery efforts. Discovery of novel protein modifications is also expected from such large scale population proteomics, expanding the protein knowledge database. In regard to cancer protein biomarkers, their validation via population proteomics-based approaches is advantageous as mass spectrometry detection is used both in the discovery and validation process, which is essential for the detection of those structurally modified protein biomarkers.

Journal Link | PMID

Comment

A nice illustration of the proteomics approach with a rational tie-in to population genetics approaches to identifying disease characteristics..