Phylogeny-based Protein Function Prediction
SIFTER (Statistical Inference of Function Through Evolutionary Relationships) is a statistical approach to predicting protein function that uses a protein family's phylogenetic tree, as the natural structure for representing protein relationships.
We are awash in proteins discovered through high-throughput sequencing projects. As only a minuscule fraction of these have been experimentally characterized, computational methods are widely used for automated annotation. Unfortunately, these predictions have littered the databases with erroneous information, for a variety of reasons including the propagation of errors and the systematic flaws in BLAST and related methods. We have developed a statistical approach to predicting protein function that uses a protein family's phylogenetic tree, as the natural structure for representing protein relationships1,2. We overlay on this all known protein functions in the family. We use a model of function evolution to then infer the functions of all other protein functions. Even our initial implementations of this method, called SIFTER (Statistical Inference of Function Through Evolutionary Relationships) have performed better than other methods in widespread use. SIFTER was recently honored as the best-performing sequence-based method in the Critical Assessment of Function Annotation 3,4.
Genome-Scale implementation of SIFTER
1. Engelhardt BE, Jordan MI, Srouji JR, Brenner SE. 2011. Genome-scale phylogenetic function annotation of large and diverse protein families.Genome Research 21:1969-1980. doi:10.1101/gr.104687.109 [PDF 1.2M]
2. Engelhardt BE, Jordan MI, Muratore KE, Brenner SE. 2005. Protein molecular function prediction by Bayesian phylogenomics. PLoS Computational Biology 1:e45. doi:10.1371/journal.pcbi.0010045 [PDF 1.4M]
3. Radivojac P, et al. 2013. A large-scale evaluation of computational protein function prediction. Nature Methods 10:221-227. doi:10.1038/nmeth.2340 [PDF 720K]
4. Sahraeian SME, Luo KR, Brenner SE. 2015. SIFTER search: a web server for accurate phylogeny-based protein function prediction. Nucleic Acids Research 43:W141-W147. doi:10.1093/nar/gkv461
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