title: Next-generation diagnostics and disease-gene discovery with the Exomiser.
abstract: Exomiser is an application that prioritizes genes and variants in next-generation sequencing (NGS) projects for novel disease-gene discovery or differential diagnostics of Mendelian disease. Exomiser comprises a suite of algorithms for prioritizing exome sequences using random-walk analysis of protein interaction networks, clinical relevance and cross-species phenotype comparisons, as well as a wide range of other computational filters for variant frequency, predicted pathogenicity and pedigree analysis. In this protocol, we provide a detailed explanation of how to install Exomiser and use it to prioritize exome sequences in a number of scenarios. Exomiser requires ∼3 GB of RAM and roughly 15-90 s of computing time on a standard desktop computer to analyze a variant call format (VCF) file. Exomiser is freely available for academic use from http://www.sanger.ac.uk/science/tools/exomiser.
authors.affiliation: Skarnes Faculty Group, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Damian
authors.initials: D
authors.lastname: Smedley
authors.affiliation: Skarnes Faculty Group, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Julius O B
authors.identifier: http://orcid.org/0000-0002-3265-1591
authors.initials: JO
authors.lastname: Jacobsen
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marten
authors.initials: M
authors.lastname: Jäger
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0002-5316-1399
authors.initials: S
authors.lastname: Köhler
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Berlin Institute for Health, Berlin, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Holtgrewe
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Schubach
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Berlin Institute for Health, Berlin, Germany.|Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Enrico
authors.initials: E
authors.lastname: Siragusa
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.|Labor Berlin - Charité Vivantes, Humangenetik, Berlin, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zemojtel
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.|Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Orion J
authors.identifier: http://orcid.org/0000-0002-9064-092X
authors.initials: OJ
authors.lastname: Buske
authors.affiliation: Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Washington
authors.affiliation: The National Institutes of Health (NIH) Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Bone
authors.affiliation: Department of Medical Informatics and Clinical Epidemiology, Oregon Health &Science University, Portland, Oregon, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Haendel
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.|Max Planck Institute for Molecular Genetics, Berlin, Germany.|Department of Mathematics and Computer Science, Institute for Bioinformatics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Peter N
authors.identifier: http://orcid.org/0000-0002-0736-9199
authors.initials: PN
authors.lastname: Robinson
mesh_terms: D059472:Exome; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods; D012984:Software