Development of the variant calling algorithm, ADIScan, and its use to estimate discordant sequences between monozygotic twins
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Cho, Yangrae; Lee, Sunho; Hong, Jong Hui; Kim, Byong Joon; Hong, Woon-Young; Jung, Jongcheol; Jung, Jongsun] Syntekabio Inc, Techno-2ro B-512, Daejeon 34025, South Korea; [Cho, Yangrae; Lee, Hyang Burm] Chonnam Natl Univ, CALS, DFTBA, Gwangju 61186, South Korea; [Lee, Sunho] Seoul Natl Univ, Sch Comp Sci & Engn, Seoul 151742, South Korea; [Hong, Jong Hui] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 08826, South Korea; [Sung, Joohon] Seoul Natl Univ, Sch Publ Hlth, Dept Epidemiol, Complex Dis & Genome Epidemiol Branch, Seoul 08826, South Korea; [Kim, Han-Na; Kim, Hyung-Lae] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul 07985, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 OXFORD UNIV PRESS
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000155722
- 본문언어 영어
- Published As http://dx.doi.org/10.1093/nar/gky445
초록/요약
Calling variants from next-generation sequencing (NGS) data or discovering discordant sequences between two NGS data sets is challenging. We developed a computer algorithm, ADIScan1, to call variants by comparing the fractions of allelic reads in a tester to the universal reference genome. We then created ADIScan2 by modifying the algorithm to directly compare two sets of NGS data and predict discordant sequences between two testers. ADIScan1 detected >99.7% of variants called by GATK with an additional 724 393 SNVs. ADIScan2 identified similar to 500 candidates of discordant sequences in each of two pairs of the monozygotic twins. About 200 of these candidates were included in the similar to 2800 predicted by VarScan2. We verified 66 true discordant sequences among the candidates that ADIScan2 and VarScan2 exclusively predicted. ADIScan2 detected many discordant sequences overlooked by VarScan2 and Mutect, which specialize in detecting low frequency mutations in genetically heterogeneous cancerous tissues. Numbers of verified sequences alone were >5 times more than expected based on recently estimated mutation rates from whole genome sequences. Estimated post-zygotic mutation rates were 1.68 x 10(-7) in this study. ADIScan1 and 2 would complement existing tools in screening causative mutations of diverse genetic diseases and comparing two sets of genome sequences, respectively.
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