Maximizing the Utility of Orthologs and Phylogenetic Profiles for Systems-Scale Comparative Genomics

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Harvard University is awarded a grant to develop a freely available, web-accessible system that makes comparative genomics data maximally available and accurately decoded into forms that facilitate further biological investigation at the scale of entire genomes. Specifically, the project will build the largest ortholog repository to date using an improved algorithm for identifying orthologs, based on appropriate evolutionary metrics of similarity. Whole-genome orthology data will be aggregated into matrices of phylogenetic profiles, enabling a series of meta-analyses including the reconstruction of genome phylogenies, and analysis of protein function and network organization. The project's specific tasks include (1) Development of an optimized algorithm to amass a database of orthologs and evolutionary distances for all available fully sequenced genomes that includes results from a maximally informative parameter space; (2) Development of a platform that allows a user to aggregate all of the above orthology data into matrices of phylogenetic profiles and, importantly, to use these matrices to study protein function, network organization and genomic evolution; and (3)Development of a graphical user interface to allow easy access to this resource by researchers world-wide from any web browser. The final product will be a tool to enable any research biologist, regardless of computational expertise, to conduct large-scale comparative genomics investigations that probe functional relationships among genes or phylogenetic relationships among genomes. Its value as a tool for training in comparative genomics and systems biology will be actively promoted through a four-part plan involving training workshops, virtual train materials on the project web page, tutorials associated with major biocomputing symposia, and new course offerings in the Department of Systems Biology at Harvard Medical School.