Indel variant analysis of short-read sequencing data with Scalpel

Fang et al . describe a computational protocol to accurately call indels from whole-genome and whole-exome sequencing data using Scalpel. Important issues for indel identification, such as short repeat regions and varying sequencing coverage, are discussed. As the second most common type of variatio...

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Published in	Nature protocols Vol. 11; no. 12; pp. 2529 - 2548
Main Authors	Fang, Han, Bergmann, Ewa A, Arora, Kanika, Vacic, Vladimir, Zody, Michael C, Iossifov, Ivan, O'Rawe, Jason A, Wu, Yiyang, Jimenez Barron, Laura T, Rosenbaum, Julie, Ronemus, Michael, Lee, Yoon-ha, Wang, Zihua, Dikoglu, Esra, Jobanputra, Vaidehi, Lyon, Gholson J, Wigler, Michael, Schatz, Michael C, Narzisi, Giuseppe
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 01.12.2016 Nature Publishing Group
Subjects	13/100 13/31 14/63 631/114/2785 631/1647/794 631/208/212 631/208/514/2254 631/208/726/649 Algorithms Alleles Analytical Chemistry Annotations Autism Biological Techniques Computational Biology/Bioinformatics Computer applications DNA Mutational Analysis - methods DNA sequencing Gene mapping Gene mutation Gene sequencing Genetic variation Genomes Genomics High-Throughput Nucleotide Sequencing - methods Humans Identification and classification INDEL Mutation Life Sciences Methods Microarrays Molecular Sequence Annotation Mutation Organic Chemistry Polymorphism, Single Nucleotide protocol Source code New York United States > US
Online Access	Get full text
ISSN	1754-2189 1750-2799 1750-2799
DOI	10.1038/nprot.2016.150

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Abstract	Fang et al . describe a computational protocol to accurately call indels from whole-genome and whole-exome sequencing data using Scalpel. Important issues for indel identification, such as short repeat regions and varying sequencing coverage, are discussed. 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.
AbstractList	Fang et al . describe a computational protocol to accurately call indels from whole-genome and whole-exome sequencing data using Scalpel. Important issues for indel identification, such as short repeat regions and varying sequencing coverage, are discussed. 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. Fang et al. describe a computational protocol to accurately call indels from whole-genome and whole-exome sequencing data using Scalpel. Important issues for indel identification, such as short repeat regions and varying sequencing coverage, are discussed.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. 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 [similar]5 h after read mapping. 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. 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.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. 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. 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 ( Keywords: Insertion and deletion, Indel, scalpel, indel detection, indel calling, exome sequencing, whole genome sequencing, short tandem repeats, repeat regions, variant calling, BWA-MEM, de Bruijn assembly, structural variant, Annovar
Audience	Academic
Author	Iossifov, Ivan Bergmann, Ewa A Schatz, Michael C Zody, Michael C Arora, Kanika Ronemus, Michael O'Rawe, Jason A Vacic, Vladimir Lyon, Gholson J Dikoglu, Esra Lee, Yoon-ha Jimenez Barron, Laura T Wang, Zihua Rosenbaum, Julie Wu, Yiyang Wigler, Michael Narzisi, Giuseppe Fang, Han Jobanputra, Vaidehi
AuthorAffiliation	7 Department of Computer Science, Johns Hopkins University, Baltimore, Maryland, USA 6 Columbia University Medical Center, New York, New York, USA 5 Centro de Ciencias Genomicas, Universidad Nacional Autonoma de Mexico, Cuernavaca, Mexico 4 New York Genome Center, New York, New York, USA 1 Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA 2 Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA 3 Stony Brook University, Stony Brook, New York, USA
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/27854363$$D View this record in MEDLINE/PubMed
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Snippet	Fang et al . describe a computational protocol to accurately call indels from whole-genome and whole-exome sequencing data using Scalpel. Important issues for... 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... Fang et al. describe a computational protocol to accurately call indels from whole-genome and whole-exome sequencing data using Scalpel. Important issues for...
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Title	Indel variant analysis of short-read sequencing data with Scalpel
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