RT Journal Article SR Electronic T1 Accurate detection of de novo and transmitted INDELs within exome-capture data using micro-assembly JF bioRxiv FD Cold Spring Harbor Laboratory SP 001370 DO 10.1101/001370 A1 Giuseppe Narzisi A1 Jason A. O’Rawe A1 Ivan Iossifov A1 Han Fang A1 Yoon-ha Lee A1 Zihua Wang A1 Yiyang Wu A1 Gholson J. Lyon A1 Michael Wigler A1 Michael C. Schatz YR 2014 UL http://biorxiv.org/content/early/2014/06/18/001370.abstract AB 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 >10000 simulated and >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.