RT Journal Article SR Electronic T1 Indel variant analysis of short-read sequencing data with Scalpel JF bioRxiv FD Cold Spring Harbor Laboratory SP 028050 DO 10.1101/028050 A1 Han Fang A1 Ewa A. Grabowska A1 Kanika Arora A1 Vladimir Vacic A1 Michael C. Zody A1 Ivan Iossifov A1 Jason A. O’Rawe A1 Yiyang Wu A1 Laura T Jimenez Barron A1 Julie Rosenbaum A1 Michael Ronemus A1 Yoon-ha Lee A1 Zihua Wang A1 Gholson J. Lyon A1 Michael Wigler A1 Michael C. Schatz A1 Giuseppe Narzisi YR 2015 UL http://biorxiv.org/content/early/2015/10/01/028050.abstract AB As the second most common type of variations in the human genome, insertions and deletions (indels) have been linked to many diseases, but indels of more than a few bases are still challenging to discover from short-read sequencing data. Scalpel (http://scalpel.sourceforge.net) is open-source software for reliable indel detection based on the micro-assembly technique. To date, it has been successfully used to discover mutations in novel candidate genes for autism, and 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 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 for 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 finished in ~6 hours after read mapping.