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Protein networks—built by association

Nature Biotechnology volume 18, pages 1242–1243 (2000)Cite this article

The total genome sequence era has provided complete catalogs of the genes of several organisms and offered the challenge of understanding the functions of large numbers of previously uncharacterized proteins. Historically, the functions of genes (i.e., their encoded proteins) have been determined by analysis of mutant phenotypes, genetic interactions, biochemical activities, homology to other proteins of known function, and physical interactions with other proteins. Schwikowski et al.1 have compiled comprehensive protein–protein interaction data sets from the yeast community and find that these interactions form one large network of 2,358 interactions among 1,548 proteins and several smaller networks. Analysis of these networks allows assignment of potential function to uncharacterized proteins and the discovery of potential interactions within and across cellular processes and compartments. These connections represent a gold mine for formulating and experimentally testing specific hypotheses about gene function.

The total genome sequence era has also made possible the ongoing development (and validation) of methodologies that address gene function on a genome-wide scale (functional genomics)2. Several new approaches are aimed at determining the function of large sets of proteins and defining how these macromolecules interact within complex networks. These include computational biology driven approaches, such as correlated phylogenetic profiles (which predict that proteins that function in a common pathway or complex will evolve in a similar fashion and be either preserved or eliminated in a given genome)3, structure-based functional genomics (which aims to assign functions to uncharacterized proteins based on structure prediction), and the analysis of domain fusion events (which is based on the premise that two domains that are fused in one organism are likely to interact in another organism in which both domains are in separate proteins)4,5. Functional assignments for newly discovered proteins have also been made by partnering them with proteins of “known” function by analyzing large experimental data sets for co-regulation of messenger RNA expression (DNA microarrays, SAGE) or protein–protein interactions (two-hybrid analysis, mass spectrometry). Not surprisingly, the best success rates at predicting functions for uncharacterized proteins come from combining several of these approaches6.

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Figure 1: Enhanced protein function prediction via an annotated protein interaction web.

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Authors and Affiliations

  1. Department of Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, 21205, MD, Baltimore

    Melanie L. Mayer & Philip Hieter

  2. Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, BC, Canada

    Melanie L. Mayer & Philip Hieter

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  1. Melanie L. Mayer
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  2. Philip Hieter
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Mayer, M., Hieter, P. Protein networks—built by association. Nat Biotechnol 18, 1242–1243 (2000). https://doi.org/10.1038/82342

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