HIGHLY SPECIFIC PROTEIN-SEQUENCE MOTIFS FOR GENOME ANALYSIS

We present a method for discovering conserved sequence motifs from fam ilies of aligned protein sequences. The method has been implemented as a computer program called EMOTIF (http://motif.stanford.edu/emotif), Given an aligned set of protein sequences, EMOTIF generates a set of m otifs with a wide range of specificities and sensitivities. EMOTIF als o can generate motifs that describe possible subfamilies of a protein superfamily, A disjunction of such motifs often can represent the enti re superfamily with high specificity and sensitivity. We have used EMO TIF to generate sets of motifs from all 7,000 protein alignments in th e BLOCKS and PRINTs databases. The resulting database, called IDENTIFY (http://motif.stanford.edu/identify), contains more than 50,000 motif s. For each alignment, the database contains several motifs having a p robability of matching a false positive that range from 10(-10) to 10( -5). Highly specific motifs are well suited for searching entire prote omes, while generating very few false predictions. IDENTIFY assigns bi ological functions to 25-30% of all proteins encoded by the Saccharomy ces cerevisiae genome and by several bacterial genomes, In particular, IDENTIFY assigned functions to 172 of proteins of unknown function in the yeast genome.