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Abstract 3IN SILICO PREDICTION OF ESCAPE MUTANTS OF THE HIV-1 PROTEASE -

Motivation: Since the availability of a huge number of sequences, comparative genomics is a central step in many sequence analysis studies. For instance, it is used to help identify regions of interest in DNA sequences, to study evolution at the molecular level (speciation events, gene duplications, whole genome duplication, etc.), to determine phylogeny of species or to predict the function of a new gene. In that context we developed a set of three homologous gene families databases that can be used in many aspects of comparative genomics. Those databases – HOVERGEN, HOGENOM and HOMOLENS – share the same architecture, and they include protein and nucleotide sequences, alignments and phylogenetic trees. Methods: The databases are built using protein sequences from different sources. HOVERGEN contains vertebrate sequences taken from UniProt. HOGENOM is devoted to completely sequenced organisms, and its sequences come from various sources (Genome Reviews, JGI, Ensembl, Bacterial species from the NCBI, etc.) HOMOLENS is devoted to the completely sequenced eukaryotes found in Ensembl. For the three systems, protein sequences are clustered into homologous families, and then alignments and trees are built on those families. The large-scale similarity searches required to cluster sequences, as well as the massive alignments and tree computations, are performed on a cluster containing more than 2000 CPUs. Lastly, phylogenetic trees are reconciled with a reference species tree. Results: The three databases can be fully downloaded from the PBIL (Pôle Bioinformatique Lyonnais) site (http://pbil.univ-lyon1.fr). On-line access is also provided through three different ways: query forms on the PBIL site, a general retrieval system (Query) and a devoted client-server graphical interface (FamFetch). The later can be used to perform tree-patterns based searches allowing, among other uses, to retrieve easily set of orthologous genes thanks to phylogenetic criteria.