title: MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer.
abstract: The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects.
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA mutalign@gmail.com.
authors.forename: Nicholas Paul
authors.initials: NP
authors.lastname: Gauthier
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ed
authors.initials: E
authors.lastname: Reznik
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jianjiong
authors.initials: J
authors.lastname: Gao
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Selcuk Onur
authors.initials: SO
authors.lastname: Sumer
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schultz
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA mutalign@gmail.com.
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.affiliation: Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK mutalign@gmail.com.
authors.forename: Martin L
authors.identifier: http://orcid.org/0000-0003-3161-8690
authors.initials: ML
authors.lastname: Miller
mesh_terms: D030541:Databases, Genetic; D023281:Genomics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D016415:Sequence Alignment; D012984:Software