title: Indel variant analysis of short-read sequencing data with Scalpel.
abstract: As the second most common type of variation in the human genome, insertions and deletions (indels) have been linked to many diseases, but the discovery of indels of more than a few bases in size from short-read sequencing data remains challenging. Scalpel (http://scalpel.sourceforge.net) is an open-source software for reliable indel detection based on the microassembly technique. It has been successfully used to discover mutations in novel candidate genes for autism, and it is extensively used in other large-scale studies of human diseases. This protocol gives an overview of the algorithm and describes how to use Scalpel to perform highly accurate indel calling from whole-genome and whole-exome sequencing data. We provide detailed instructions for an exemplary family-based de novo study, but we also characterize the other two supported modes of operation: single-sample and somatic analysis. Indel normalization, visualization and annotation of the mutations are also illustrated. Using a standard server, indel discovery and characterization in the exonic regions of the example sequencing data can be completed in ∼5 h after read mapping.
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Stony Brook University, Stony Brook, New York, USA.
authors.forename: Han
authors.identifier: http://orcid.org/0000-0002-4010-2525
authors.initials: H
authors.lastname: Fang
authors.affiliation: New York Genome Center, New York, New York, USA.
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Bergmann
authors.affiliation: New York Genome Center, New York, New York, USA.
authors.forename: Kanika
authors.initials: K
authors.lastname: Arora
authors.affiliation: New York Genome Center, New York, New York, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vacic
authors.affiliation: New York Genome Center, New York, New York, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Zody
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Iossifov
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Stony Brook University, Stony Brook, New York, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: O'Rawe
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Stony Brook University, Stony Brook, New York, USA.
authors.forename: Yiyang
authors.identifier: http://orcid.org/0000-0002-9231-7093
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Centro de Ciencias Genomicas, Universidad Nacional Autonoma de Mexico, Cuernavaca, Mexico.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Jimenez Barron
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Rosenbaum
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ronemus
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Yoon-Ha
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Esra
authors.initials: E
authors.lastname: Dikoglu
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Columbia University Medical Center, New York, New York, USA.
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Stony Brook University, Stony Brook, New York, USA.
authors.forename: Gholson J
authors.identifier: http://orcid.org/0000-0002-5869-0716
authors.initials: GJ
authors.lastname: Lyon
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|Department of Computer Science, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Schatz
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.|New York Genome Center, New York, New York, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Narzisi
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis / Q000379:methods*; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D054643:INDEL Mutation; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide