TY - JOUR T1 - Accurate detection of <em>de novo</em> and transmitted INDELs within exome-capture data using micro-assembly JF - bioRxiv DO - 10.1101/001370 SP - 001370 AU - Giuseppe Narzisi AU - Jason A. O’Rawe AU - Ivan Iossifov AU - Han Fang AU - Yoon-ha Lee AU - Zihua Wang AU - Yiyang Wu AU - Gholson J. Lyon AU - Michael Wigler AU - Michael C. Schatz Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/06/18/001370.abstract N2 - We present a new open-source algorithm, Scalpel, for sensitive and specific discovery of INDELs in exome-capture data. By combining the power of mapping and assembly, Scalpel carefully searches the de Bruijn graph for sequence paths that span each exon. A detailed repeat analysis coupled with a self-tuning k-mer strategy allows Scalpel to outperform other state-of-the-art approaches for INDEL discovery. We extensively compared Scalpel with a battery of &gt;10000 simulated and &gt;1000 experimentally validated INDELs against two recent algorithms: GATK HaplotypeCaller and SOAPindel. We report anomalies for these tools to detect INDELs in regions containing near-perfect repeats. We also present a large-scale application of Scalpel for detecting de novo and transmitted INDELs in 593 families from the Simons Simplex Collection. Scalpel demonstrates enhanced power to detect long (≥20bp) transmitted events, and strengthens previous reports of enrichment for de novo likely gene-disrupting INDELs in autistic children with many new candidate genes. ER -