RT Journal A1 Thomas, Paul D. A1 Campbell, Michael J. A1 Kejariwal, Anish A1 Mi, Huaiyu A1 Karlak, Brian A1 Daverman, Robin A1 Diemer, Karen A1 Muruganujan, Anushya A1 Narechania, Apurva T1 PANTHER: A Library of Protein Families and Subfamilies Indexed by Function JF Genome Research JO Genome Research YR 2003 FD September 01 VO 13 IS 9 SP 2129 OP 2141 DO 10.1101/gr.772403 UL http://genome.cshlp.org/content/13/9/2129.abstract AB In the genomic era, one of the fundamental goals is to characterize the function of proteins on a large scale. We describe a method, PANTHER, for relating protein sequence relationships to function relationships in a robust and accurate way. PANTHER is composed of two main components: the PANTHER library (PANTHER/LIB) and the PANTHER index (PANTHER/X). PANTHER/LIB is a collection of “books,” each representing a protein family as a multiple sequence alignment, a Hidden Markov Model (HMM), and a family tree. Functional divergence within the family is represented by dividing the tree into subtrees based on shared function, and by subtree HMMs. PANTHER/X is an abbreviated ontology for summarizing and navigating molecular functions and biological processes associated with the families and subfamilies. We apply PANTHER to three areas of active research. First, we report the size and sequence diversity of the families and subfamilies, characterizing the relationship between sequence divergence and functional divergence across a wide range of protein families. Second, we use the PANTHER/X ontology to give a high-level representation of gene function across the human and mouse genomes. Third, we use the family HMMs to rank missense single nucleotide polymorphisms (SNPs), on a database-wide scale, according to their likelihood of affecting protein function.