title: StructMAn: annotation of single-nucleotide polymorphisms in the structural context.
abstract: The next generation sequencing technologies produce unprecedented amounts of data on the genetic sequence of individual organisms. These sequences carry a substantial amount of variation that may or may be not related to a phenotype. Phenotypically important part of this variation often comes in form of protein-sequence altering (non-synonymous) single nucleotide variants (nsSNVs). Here we present StructMAn, a Web-based tool for annotation of human and non-human nsSNVs in the structural context. StructMAn analyzes the spatial location of the amino acid residue corresponding to nsSNVs in the three-dimensional (3D) protein structure relative to other proteins, nucleic acids and low molecular-weight ligands. We make use of all experimentally available 3D structures of query proteins, and also, unlike other tools in the field, of structures of proteins with detectable sequence identity to them. This allows us to provide a structural context for around 20% of all nsSNVs in a typical human sequencing sample, for up to 60% of nsSNVs in genes related to human diseases and for around 35% of nsSNVs in a typical bacterial sample. Each nsSNV can be visualized and inspected by the user in the corresponding 3D structure of a protein or protein complex. The StructMAn server is available at http://structman.mpi-inf.mpg.de.
authors.affiliation: Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbrücken, Germany Graduate School of Computer Science, Saarland University, Campus E1 3, 66123 Saarbrücken, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gress
authors.affiliation: Center for Neurobehavioral Genetics, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
authors.forename: Vasily
authors.initials: V
authors.lastname: Ramensky
authors.affiliation: Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbrücken, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Büch
authors.affiliation: Chair for Medical Bioinformatics, Saarland University, Campus E2 2, 66123 Saarbrücken, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.affiliation: Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbrücken, Germany kalinina@mpi-inf.mpg.de.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kalinina
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000235:genetics; D019985:Benchmarking; D004194:Disease / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D000077156:Gefitinib; D006801:Humans; D021621:Imaging, Three-Dimensional; D020407:Internet; D008024:Ligands; D008958:Models, Molecular; D058977:Molecular Sequence Annotation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D011799:Quinazolines / Q000494:pharmacology; D012984:Software
chemical_list: D000596:Amino Acids; D008024:Ligands; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib