Abstract
As the protein databases continue to expand at an exponential rate, fed by daily uploads from multiple large scale genomic and metagenomic projects, the problem of assigning a function to each new protein has become the focus of significant research interest in recent times. Herein, we review the most recent advances in the field of automated function prediction (AFP). We begin by defining what is meant by biological “function” and the means of describing such functions using standardised machine readable ontologies. We then focus on the various function-prediction programs available, both sequence and structure based, and outline their associated strengths and weaknesses. Finally, we conclude with a brief overview of the future challenges and outstanding questions in the field, which still remain unanswered.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Altschul SF et al (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
Ashburner M, Lewis S (2002) On ontologies for biologists: the Gene Ontology–untangling the web. Novartis Found Symp 247: 66–80; discussion 80–63, 84–90, 244–252
Attwood TK et al (2003) PRINTS and its automatic supplement, prePRINTS. Nucleic Acids Res 31:400–402
Bork P (2000) Powers and pitfalls in sequence analysis: the 70% hurdle. Genome Res 10:398–400
Breitkreutz BJ, Stark C, Tyers M (2003) The GRID: the general repository for interaction datasets. Genome Biol 4:R23
Di Gennaro JA et al (2001) Enhanced functional annotation of protein sequences via the use of structural descriptors. J Struct Biol 134:232–245
Eisenberg D, Marcotte EM, Xenarios I, Yeates TO (2000) Protein function in the post-genomic era. Nature 405:823–826
Enault F, Suhre K, Claverie JM (2005) Phydbac “Gene Function Predictor”: a gene annotation tool based on genomic context analysis. BMC Bioinformatics 6:247
Friedberg I (2006) Automated protein function prediction–the genomic challenge. Brief Bioinform 7:225–242
Galperin MY, Walker DR, Koonin EV (1998) Analogous enzymes: independent inventions in enzyme evolution. Genome Res 8:779–790
Gibrat JF, Madej T, Bryant SH (1996) Surprising similarities in structure comparison. Curr Opin Struct Biol 6:377–385
Gilks WR, Audit B, de Angelis D, Tsoka S, Ouzounis CA (2005) Percolation of annotation errors through hierarchically structured protein sequence databases. Math Biosci 193:223–234
Godzik A, Jambon M, Friedberg I (2007) Computational protein function prediction: are we making progress? Cell Mol Life Sci 64:2505–2511
Goldsmith-Fischman S, Honig B (2003) Structural genomics: computational methods for structure analysis. Protein Sci 12:1813–1821
Henikoff JG, Greene EA, Pietrokovski S, Henikoff S (2000) Increased coverage of protein families with the blocks database servers. Nucleic Acids Res 28:228–230
Hulo N et al (2008) The 20 years of PROSITE. Nucleic Acids Res 36:D245–D249
Jeffery CJ (2003) Moonlighting proteins: old proteins learning new tricks. Trends Genet 19:415–417
Jones S, Thornton JM (2004) Searching for functional sites in protein structures. Curr Opin Chem Biol 8:3–7
Laskowski RA, Watson JD, Thornton JM (2003) From protein structure to biochemical function? J Struct Funct Genomics 4:167–177
Lehne B, Schlitt T (2009) Protein-protein interaction databases: keeping up with growing interactomes. Hum Genomics 3:291–297
Losko S, Heumann K (2009) Semantic data integration and knowledge management to represent biological network associations. Methods Mol Biol 563:241–258
Rost B (2002) Enzyme function less conserved than anticipated. J Mol Biol 318:595–608
Rost B, Liu J, Nair R, Wrzeszczynski KO, Ofran Y (2003) Automatic prediction of protein function. Cell Mol Life Sci 60:2637–2650
Sharan R, Ulitsky I, Shamir R (2007) Network-based prediction of protein function. Mol Syst Biol 3:88
Sleator RD, Shortall C, Hill C (2008) Metagenomics. Lett Appl Microbiol 47:361–366
Smith CL, Goldsmith CA, Eppig JT (2005) The mammalian phenotype ontology as a tool for annotating, analyzing and comparing phenotypic information. Genome Biol 6:R7
Taubig H, Buchner A, Griebsch J (2006) PAST: fast structure-based searching in the PDB. Nucleic Acids Res 34:W20–W23
Todd AE, Orengo CA, Thornton JM (2001) Evolution of function in protein superfamilies, from a structural perspective. J Mol Biol 307:1113–1143
Walker MG, Volkmuth W, Sprinzak E, Hodgson D, Klingler T (1999) Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes. Genome Res 9:1198–1203
Wallace AC, Laskowski RA, Thornton JM (1996) Derivation of 3D coordinate templates for searching structural databases: application to Ser-His-Asp catalytic triads in the serine proteinases and lipases. Protein Sci 5:1001–1013
Watson JD, Laskowski RA, Thornton JM (2005) Predicting protein function from sequence and structural data. Curr Opin Struct Biol 15:275–284
Ye Y, Godzik A (2004) FATCAT: a web server for flexible structure comparison and structure similarity searching. Nucleic Acids Res 32:W582–W585
Zhao XM, Chen L, Aihara K (2008) Protein function prediction with high-throughput data. Amino Acids 35:517–530
Acknowledgments
The authors wish to acknowledge the financial assistance of the Faculty of Engineering and Science, the Department of Biological Sciences and the Department of Computing at Cork Institute of Technology.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by Erko Stackebrandt.
Rights and permissions
About this article
Cite this article
Sleator, R.D., Walsh, P. An overview of in silico protein function prediction. Arch Microbiol 192, 151–155 (2010). https://doi.org/10.1007/s00203-010-0549-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00203-010-0549-9