Fast and accurate mutation detection in whole genome sequences of multiple isogenic samples with IsoMut

Pipek, O. and Ribli, D. and Molnár, János and Póti, Á. and Krzystanek, M. and Tusnády, Gábor and Szüts, Dávid (2017) Fast and accurate mutation detection in whole genome sequences of multiple isogenic samples with IsoMut. BMC BIOINFORMATICS, 18 (1). p. 73. ISSN 1471-2105


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Background: Detection of somatic mutations is one of the main goals of next generation DNA sequencing. A wide range of experimental systems are available for the study of spontaneous or environmentally induced mutagenic processes. However, most of the routinely used mutation calling algorithms are not optimised for the simultaneous analysis of multiple samples, or for non-human experimental model systems with no reliable databases of common genetic variations. Most standard tools either require numerous in-house post filtering steps with scarce documentation or take an unpractically long time to run. To overcome these problems, we designed the streamlined IsoMut tool which can be readily adapted to experimental scenarios where the goal is the identification of experimentally induced mutations in multiple isogenic samples. Methods: Using 30 isogenic samples, reliable cohorts of validated mutations were created for testing purposes. Optimal values of the filtering parameters of IsoMut were determined in a thorough and strict optimization procedure based on these test sets. Results: We show that IsoMut, when tuned correctly, decreases the false positive rate compared to conventional tools in a 30 sample experimental setup; and detects not only single nucleotide variations, but short insertions and deletions as well. IsoMut can also be run more than a hundred times faster than the most precise state of art tool, due its straightforward and easily understandable filtering algorithm. Conclusions: IsoMut has already been successfully applied in multiple recent studies to find unique, treatment induced mutations in sets of isogenic samples with very low false positive rates. These types of studies provide an important contribution to determining the mutagenic effect of environmental agents or genetic defects, and IsoMut turned out to be an invaluable tool in the analysis of such data. © 2017 The Author(s).

Item Type: Article
Additional Information: N1 Funding details: OTKA K104586, OTKA, Országos Tudományos Kutatási Alapprogramok N1 Funding text: This work was supported by Momentum Grant LP2011-015 of the Hungarian Academy of Sciences to DS and a Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant no. NNF15OC0016584 to ZS and IC. ZS is supported by the Breast Cancer Research Foundation, Basser Foundation and the Széchenyi Progam, Hungary (KTIA_NAP_13-2014-0021). GET is supported by Momentum Grant LP2012-035 of the Hungarian Academy of Sciences. GET and JM are also supported by the Hungarian Scientific Research Fund (OTKA K104586). IC, AB, DR and OP are supported by the European Commission H2020 program under contract number 643476 (
Uncontrolled Keywords: Optimization; Whole genome sequences; somatic mutation; Optimization procedures; Next-generation sequencing; Next-generation dna sequencing; Isogenic; Insertions and deletions; False positive rates; Gene encoding; DNA sequences; Somatic mutation detection; Next generation sequencing; MUTAGENESIS; Multiple isogenic samples; Low false positive rate; Demonstrative algorithm
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 20 Feb 2017 11:44
Last Modified: 20 Feb 2017 11:44

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