title: ProtPhylo: identification of protein-phenotype and protein-protein functional associations via phylogenetic profiling.
abstract: ProtPhylo is a web-based tool to identify proteins that are functionally linked to either a phenotype or a protein of interest based on co-evolution. ProtPhylo infers functional associations by comparing protein phylogenetic profiles (co-occurrence patterns of orthology relationships) for more than 9.7 million non-redundant protein sequences from all three domains of life. Users can query any of 2048 fully sequenced organisms, including 1678 bacteria, 255 eukaryotes and 115 archaea. In addition, they can tailor ProtPhylo to a particular kind of biological question by choosing among four main orthology inference methods based either on pair-wise sequence comparisons (One-way Best Hits and Best Reciprocal Hits) or clustering of orthologous proteins across multiple species (OrthoMCL and eggNOG). Next, ProtPhylo ranks phylogenetic neighbors of query proteins or phenotypic properties using the Hamming distance as a measure of similarity between pairs of phylogenetic profiles. Candidate hits can be easily and flexibly prioritized by complementary clues on subcellular localization, known protein-protein interactions, membrane spanning regions and protein domains. The resulting protein list can be quickly exported into a csv text file for further analyses. ProtPhylo is freely available at http://www.protphylo.org.
authors.affiliation: Gene Center, Ludwig-Maximilians-University, Munich, Bavaria 81377, Germany Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Bavaria 85764, Germany.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Gene Center, Ludwig-Maximilians-University, Munich, Bavaria 81377, Germany Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Bavaria 85764, Germany perocchi@genzentrum.lmu.de.
authors.forename: Fabiana
authors.identifier: http://orcid.org/0000-0002-1102-6500
authors.initials: F
authors.lastname: Perocchi
mesh_terms: D000465:Algorithms; D015220:Calcium Channels / Q000378:metabolism; D023281:Genomics; D006801:Humans; D020407:Internet; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D025941:Protein Interaction Mapping; D011506:Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology*; D020539:Sequence Analysis, Protein; D012984:Software; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C034703:mitochondrial calcium uniporter