Wikiomics:Protein function prediction
There are now plenty of proteins which have a totally unknown function. Automated function prediction is an active research field, with a growing community of bioinformaticians as observed at the AFP-SIG that took place at the ISMB 2005 conference, and at University of California San Diego in 2006.
Most often, only the sequence of the protein is known, but there are also hundreds of protein structures of unknown function which are provided by the structural genomics centers. Sometimes the proteins come from prokaryotes where the operons make it possible to infer the function of a protein from its genomic context, but this is more complicated in eukaryotes. And more generally, it is easier to guess right when a given protein has well-described homologs than when it belongs to a family of unknown biological role.
Of course, the notion of protein function is pretty broad and cannot easily be encoded without relying on a complex vocabulary. For that matter, the Gene Ontology aka GO provides hierarchical set of keywords called GO terms which describe different aspects of protein function with different levels of precision. GO is currently imposing itself as a standard for proteome annotation and function prediction of proteins.
Among the current software tools that exist today, several main strategies can be distinguished:
- homology search and transfer of annotations:
- sequence alignment
- structure alignment
- function inference by genomic context
- phylogenomic approaches
- prediction from structure using similarities that are not homology-based:
- local sequence patterns
- physico-chemical sequence features
- 3D local sites
- 3D physico-chemical features
Servers which competed at the AFP-SIG 2005
See also the short summaries by the authors themselves at the official site of AFP-SIG 2005.
These servers are based on transfer of function based on homology:
And the other servers are:
- SpearMint and RuleBase (not public yet) 
- PhydBac [7, 8, 9, 10, 11] analyzes bacterial proteins using genomic context.
- ProKnow  searches for known 3D folds, sequences, motifs, and functional linkages
- Wikiomics:BLAST and Wikiomics:PSI-BLAST [13, 14] are commonly used to search for homologous protein sequences by sequence alignment.
- Prosite [15, 16] is a searchable database of sequence patterns that are associated with some biological functions.
Other protein function prediction servers
JAFA is a meta-server for function prediction of proteins: it produces a prediction based on an aggregate from other servers. You might want to start with JAFA since it queries 5 servers (GOFigure, GOblet, InterproScan, GOtcha, PhydBac) and shows you where their results agree and differ.
- Protein Function Prediction Server - Protein function predictions from PDB structures . An enzyme/non-enzyme predictor, and an enzyme class predictor are available.
- GoFigure  predicts the function of a gene or protein
- ProFunc [19, 20] performs predictions from a protein structure
Methods using non-sequential sequence features:
These methods are based on function transfer after homology searches:
- Blast2GO 
- OntoBlast 
- GOblet [26, 27]
- GOtcha 
- Phunctioner  is a method based on the association of GO terms with conserved residues in 3D structural alignments
- Wikiomics:Automated function prediction of genes and proteins, our local community pages
- Martí-Renom MA, Ilyin VA, and Sali A. DBAli: a database of protein structure alignments. Bioinformatics. 2001 Aug;17(8):746-7. DOI:10.1093/bioinformatics/17.8.746 |
- Hawkins T, Luban S, and Kihara D. Enhanced automated function prediction using distantly related sequences and contextual association by PFP. Protein Sci. 2006 Jun;15(6):1550-6. DOI:10.1110/ps.062153506 |
- Szafron D, Lu P, Greiner R, Wishart DS, Poulin B, Eisner R, Lu Z, Anvik J, Macdonell C, Fyshe A, and Meeuwis D. Proteome Analyst: custom predictions with explanations in a web-based tool for high-throughput proteome annotations. Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W365-71. DOI:10.1093/nar/gkh485 |
- Lu P, Szafron D, Greiner R, Wishart DS, Fyshe A, Pearcy B, Poulin B, Eisner R, Ngo D, and Lamb N. PA-GOSUB: a searchable database of model organism protein sequences with their predicted Gene Ontology molecular function and subcellular localization. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D147-53. DOI:10.1093/nar/gki120 |
- Vinayagam A, König R, Moormann J, Schubert F, Eils R, Glatting KH, and Suhai S. Applying Support Vector Machines for Gene Ontology based gene function prediction. BMC Bioinformatics. 2004 Aug 26;5:116. DOI:10.1186/1471-2105-5-116 |
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- Laskowski RA, Watson JD, and Thornton JM. ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W89-93. DOI:10.1093/nar/gki414 |
- Laskowski RA, Watson JD, and Thornton JM. Protein function prediction using local 3D templates. J Mol Biol. 2005 Aug 19;351(3):614-26. DOI:10.1016/j.jmb.2005.05.067 |
- Jensen LJ, Gupta R, Blom N, Devos D, Tamames J, Kesmir C, Nielsen H, Staerfeldt HH, Rapacki K, Workman C, Andersen CA, Knudsen S, Krogh A, Valencia A, and Brunak S. Prediction of human protein function from post-translational modifications and localization features. J Mol Biol. 2002 Jun 21;319(5):1257-65. DOI:10.1016/S0022-2836(02)00379-0 |
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- Zehetner G. OntoBlast function: From sequence similarities directly to potential functional annotations by ontology terms. Nucleic Acids Res. 2003 Jul 1;31(13):3799-803. DOI:10.1093/nar/gkg555 |
- Hennig S, Groth D, and Lehrach H. Automated Gene Ontology annotation for anonymous sequence data. Nucleic Acids Res. 2003 Jul 1;31(13):3712-5. DOI:10.1093/nar/gkg582 |
- Groth D, Lehrach H, and Hennig S. GOblet: a platform for Gene Ontology annotation of anonymous sequence data. Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W313-7. DOI:10.1093/nar/gkh406 |
- Martin DM, Berriman M, and Barton GJ. GOtcha: a new method for prediction of protein function assessed by the annotation of seven genomes. BMC Bioinformatics. 2004 Nov 18;5:178. DOI:10.1186/1471-2105-5-178 |
- Pazos F and Sternberg MJ. Automated prediction of protein function and detection of functional sites from structure. Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14754-9. DOI:10.1073/pnas.0404569101 |
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- Martin Jambon: introduction plus the initial list of tools and papers, put together after the AFP-SIG 2005 conference (at ISMB 2005)
- other Wikiomics authors