Computational overview of GPCR gene universe to support reverse chemical genomics study

In order to support high-throughput screening for ligands of G-protein coupled receptors (GPCRs) by using bioinformatics technology, we introduce a database (SEVENS) with genome-scale annotation and software (GRIFFIN) that can simulate GPCR function. SEVENS ( http://sevens.cbrc.jp/ ) is an integrated database that includes GPCR genes that are identified with high accuracy (99.4% sensitivity and 96.6% specificity) from various types of genomes, by a pipeline that integrates such software as a gene finder, a sequence alignment tool, a motif and domain assignment tool, and a transmembrane helix (TMH) predictor. SEVENS provides the user a genome-scale overview of the "GPCR universe" with detailed information of chromosomal mapping, phylogenetic tree, protein sequence and structure, and experimental evidence, all of which are accessible via a user-friendly interface. GRIFFIN ( http://griffin.cbrc.jp/ ) can predict GPCR and G-protein coupling selectivity induced by ligand binding with high sensitivity and specificity (more than 87% on average), based on the support vector machine (SVM) and hidden Markov Model (HMM). SEVENS and GRIFFIN are expected to contribute to revealing the function of orphan and unknown GPCRs.