Identifying Protein Function—A Call for Community Action

Abstract

Functional information is lacking for many of the hypothetical proteins encoded within sequenced genomes. Richard Roberts proposes that a community-based approach might offer an effecient way to fill the function gap

Identification and functional analysis of 'hypothetical' genes expressed in Haemophilus influenzae

“…Since it is unrealistic to expect that all of these genes or even a signi®cant fraction of them will be studied experimentally any time soon, the functions of these genes need to be deduced through an integrative approach, combining high-throughput methods, computational analyses and curation (10).…”

“…As the list of the`conserved hypothetical' proteins keeps growing at an escalating pace, integrative studies that combine protein and gene expression analyses, computational biology, comparative genomics, mutational analysis and curation can help in identifying the most intriguing genes in every genome (8,10). This in turn will create reasonable and veri®able hypotheses for further experimental and computational work towards better understanding of the functioning of (bacterial) cells.…”

“…The very idea that there are important genes whose functions are still obscure is quite unsettling as it reveals that there are still important gaps in our understanding of basic (micro)biology (9,10). Our recent study of the H.in¯uenzae proteome identi®ed 15`conserved hypothetical' proteins that were con®dently detected in aerobically grown cells (11) and whose genes were found to be essential in transposon mutagenesis studies (12).…”

The Future of microbial metagenomics (or is ignorance bliss?)

“…As numerous studies have shown that the general paradigm is valid, however, our knowledge of the protein universe is less than perfect. Not only are the current annotations of protein-coding genes not comprehensive, but also a large proportion of genes in newly sequenced microbes and viruses cannot be annotated (or even identified; Roberts, 2004), which severely limits our ability to use metagenomics for microbial diversity studies. Although concerted efforts are under way to improve the coverage of known genome-derived proteins from wet-lab derived biochemical annotations, the technology to link the small body of experimentally generated evidence to large 'families' of similar proteins is still in flux.…”

Protein function space: viewing the limits or limited by our view?

“…Directed community approaches for systematic large-scale experimental protein characterization must follow, as has already been proposed and initiated for genome annotation and structural proteomics [71][72][73]. Without them, functional annotation of novel proteins or families by prediction alone is difficult.…”