Systematic Analysis of Experimental Phenotype Data Reveals Gene FunctionsReportar como inadecuado

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High-throughput phenotyping projects in model organisms have the potential to improve our understanding of gene functions and their role in living organisms. We have developed a computational, knowledge-based approach to automatically infer gene functions from phenotypic manifestations and applied this approach to yeast Saccharomyces cerevisiae, nematode worm Caenorhabditis elegans, zebrafish Danio rerio, fruitfly Drosophila melanogaster and mouse Mus musculus phenotypes. Our approach is based on the assumption that, if a mutation in a gene leads to a phenotypic abnormality in a process , then must have been involved in , either directly or indirectly. We systematically analyze recorded phenotypes in animal models using the formal definitions created for phenotype ontologies. We evaluate the validity of the inferred functions manually and by demonstrating a significant improvement in predicting genetic interactions and protein-protein interactions based on functional similarity. Our knowledge-based approach is generally applicable to phenotypes recorded in model organism databases, including phenotypes from large-scale, high throughput community projects whose primary mode of dissemination is direct publication on-line rather than in the literature.

Autor: Robert Hoehndorf , Nigel W. Hardy, David Osumi-Sutherland, Susan Tweedie, Paul N. Schofield, Georgios V. Gkoutos



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