GeneSeer: A Flexible, Easy-to-Use Tool to Aid Drug Discovery by Exploring Evolutionary Relationships Between Genes Across Genomes. Douglas D. Fenger, Matthew Shaw, Philip Cheung, Tim Tully. Bioinformatics Dept, Dart NeuroScience, San Diego, CA.

   Homologous relationships are useful in drug discovery because they facilitate the mapping of gene/protein function between and within species, allowing functional predictions of novel or unknown genes. Early knowledge of a gene's paralogous family is also important when designing the safety screens associated with a drug discovery project. If the target has related paralogs, it is important that the drug discovery team understand the potential effects of an off target interaction. A drug discovery program might want to include a selectivity screen as part of their assay cascade to ensure that their drug is not binding close paralogs, resulting in undesirable off target effects. Now that genomic sequences for many species are readily available, bioinformatic algorithms can perform entire genome comparisons to identify these same relationships.
   GeneSeer (http://geneseer.com) is a publicly available tool that leverages public sequence data, gene metadata information, and other publicly available data to calculate and display orthologous and paralogous gene relationships for all genes from several species, including yeasts, insects, worms, vertebrates, mammals, and primates such as human. GeneSeer calculates homology relationships by performing a full proteome BLAST calculation between two species. The GeneSeer interface is designed to help scientists quickly predict important drug discovery attributes such as selectivity and safety. It is a useful tool for cross-species translational mapping and enables scientists to easily translate hypotheses about gene identity and function from one species to another. Besides describing GeneSeer's underlying methods and user-friendly interface, we will also present a validation study of GeneSeer versus Homologene, the homolog prediction tool from NCBI. The underlying scientific data for GeneSeer has been validated to be as good as, if not better than, Homologene. Finally, a comparison of features shows GeneSeer to be the most feature rich when compared to alternative orthologing tools.