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Testing the accuracy of eukaryotic phylogenetic profiles for prediction of biological function.

ABSTRACT: A phylogenetic profile captures the pattern of gene gain and loss throughout evolutionary time. Proteins that interact directly or indirectly within the cell to perform a biological function will often co-evolve, and this co-evolution should be well reflected within their phylogenetic profiles. Thus similar phylogenetic profiles are commonly used for grouping proteins into functional groups. However, it remains unclear how the size and content of the phylogenetic profile impacts the ability to predict function, particularly in Eukaryotes. Here we developed a straightforward approach to address this question by constructing a complete set of phylogenetic profiles for 31 fully sequenced Eukaryotes. Using Gene Ontology as our gold standard, we compared the accuracy of functional predictions made by a comprehensive array of permutations on the complete set of genomes. Our permutations showed that phylogenetic profiles containing between 25 and 31 Eukaryotic genomes performed equally well and significantly better than all other permuted genome sets, with one exception: we uncovered a core of group of 18 genomes that achieved statistically identical accuracy. This core group contained genomes from each branch of the eukaryotic phylogeny, but also contained several groups of closely related organisms, suggesting that a balance between phylogenetic breadth and depth may improve our ability to use Eukaryotic specific phylogenetic profiles for functional annotations.

SUBMITTER: Singh S

PROVIDER: S-EPMC2614202 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Testing the accuracy of eukaryotic phylogenetic profiles for prediction of biological function.

Singh Saurav S Wall Dennis P DP

Evolutionary bioinformatics online 20080618

A phylogenetic profile captures the pattern of gene gain and loss throughout evolutionary time. Proteins that interact directly or indirectly within the cell to perform a biological function will often co-evolve, and this co-evolution should be well reflected within their phylogenetic profiles. Thus similar phylogenetic profiles are commonly used for grouping proteins into functional groups. However, it remains unclear how the size and content of the phylogenetic profile impacts the ability to p ...[more]

PMID: 19204819

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Project description:A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning) that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST) have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT) dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics techniques and will help biologists systematically integrate prior knowledge from diverse systems to direct targeted experiments in their organism of study.

Dataset Information

Testing the accuracy of eukaryotic phylogenetic profiles for prediction of biological function.

Publications

Testing the accuracy of eukaryotic phylogenetic profiles for prediction of biological function.

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