title: Identifying micro-inversions using high-throughput sequencing reads.
abstract: BACKGROUND
  The identification of inversions of DNA segments shorter than read length (e.g., 100 bp), defined as micro-inversions (MIs), remains challenging for next-generation sequencing reads. It is acknowledged that MIs are important genomic variation and may play roles in causing genetic disease. However, current alignment methods are generally insensitive to detect MIs. Here we develop a novel tool, MID (Micro-Inversion Detector), to identify MIs in human genomes using next-generation sequencing reads.
  
  
  RESULTS
  The algorithm of MID is designed based on a dynamic programming path-finding approach. What makes MID different from other variant detection tools is that MID can handle small MIs and multiple breakpoints within an unmapped read. Moreover, MID improves reliability in low coverage data by integrating multiple samples. Our evaluation demonstrated that MID outperforms Gustaf, which can currently detect inversions from 30 bp to 500 bp.
  
  
  CONCLUSIONS
  To our knowledge, MID is the first method that can efficiently and reliably identify MIs from unmapped short next-generation sequencing reads. MID is reliable on low coverage data, which is suitable for large-scale projects such as the 1000 Genomes Project (1KGP). MID identified previously unknown MIs from the 1KGP that overlap with genes and regulatory elements in the human genome. We also identified MIs in cancer cell lines from Cancer Cell Line Encyclopedia (CCLE). Therefore our tool is expected to be useful to improve the study of MIs as a type of genetic variant in the human genome. The source code can be downloaded from: http://cqb.pku.edu.cn/ZhuLab/MID .
authors.affiliation: State Key Laboratory for Turbulence and Complex Systems and Department of Biomedical Engineering, and Center for Quantitative Biology, Peking University, Beijing, 100871, China. ffhe@pku.edu.cn.
authors.forename: Feifei
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Bioengineering, University of Illinois, Urbana, IL, 61801, USA. yangli9@illinois.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Applied Mathematics, Brown University, Providence, RI, 02912, USA. sisifogknight@gmail.com.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Tang
authors.affiliation: Department of Bioengineering, University of Illinois, Urbana, IL, 61801, USA. jianma@illinois.edu.|Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, IL, 61801, USA. jianma@illinois.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory for Turbulence and Complex Systems and Department of Biomedical Engineering, and Center for Quantitative Biology, Peking University, Beijing, 100871, China. hqzhu@pku.edu.cn.
authors.forename: Huaiqiu
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000465:Algorithms; D007446:Chromosome Inversion / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020407:Internet; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014584:User-Computer Interface
chemical_list: D004247:DNA
references.citation: Brief Bioinform. 2015 Sep;16(5):852-64
references.pmid: 25504367
references.citation: Nat Rev Genet. 2006 Sep;7(9):715-27
references.pmid: 16983801
references.citation: Nat Methods. 2009 Nov;6(11 Suppl):S13-20
references.pmid: 19844226
references.citation: Genome Res. 2008 Nov;18(11):1851-8
references.pmid: 18714091
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19824-9
references.pmid: 17189424
references.citation: Nat Genet. 2003 Mar;33 Suppl:228-37
references.pmid: 12610532
references.citation: Nat Methods. 2012 Mar 04;9(4):357-9
references.pmid: 22388286
references.citation: Nature. 2012 Nov 1;491(7422):56-65
references.pmid: 23128226
references.citation: PLoS Biol. 2007 Sep 4;5(10):e254
references.pmid: 17803354
references.citation: Cancer Genet. 2013 Dec;206(12):432-40
references.pmid: 24405614
references.citation: Bioinformatics. 2014 Dec 15;30(24):3484-90
references.pmid: 25028727
references.citation: BMC Evol Biol. 2011 May 25;11:141
references.pmid: 21612607
references.citation: Nat Methods. 2011 Jun 12;8(8):652-4
references.pmid: 21666668
references.citation: Am J Hum Genet. 2006 Jan;78(1):38-51
references.pmid: 16385448
references.citation: Genome Res. 2006 Dec;16(12):1557-65
references.pmid: 16983148
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Bioinformatics. 2012 Sep 15;28(18):i333-i339
references.pmid: 22962449
references.citation: Genome Res. 2012 Sep;22(9):1760-74
references.pmid: 22955987
references.citation: Brief Funct Genomics. 2015 Sep;14(5):369-79
references.pmid: 25998059
references.citation: Bioinformatics. 2012 Oct 15;28(20):2576-83
references.pmid: 22851530
references.citation: Hum Mol Genet. 2009 Oct 15;18(R2):R163-8
references.pmid: 19808792
references.citation: Bioinformatics. 2009 Nov 1;25(21):2865-71
references.pmid: 19561018
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: Nature. 2012 Mar 28;483(7391):603-7
references.pmid: 22460905
references.citation: J Med Genet. 2008 May;45(5):314-8
references.pmid: 18234729
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Nat Methods. 2009 Sep;6(9):677-81
references.pmid: 19668202
references.citation: Nat Methods. 2012 Jan 30;9(2):133-7
references.pmid: 22290183
references.citation: Genome Med. 2010 Feb 12;2(2):11
references.pmid: 20156332
references.citation: Lung Cancer. 2002 Dec;38(3):235-41
references.pmid: 12445744
references.citation: BMC Bioinformatics. 2011 Dec 14;12 Suppl 14:S7
references.pmid: 22373054
references.citation: J Intern Med. 2014 Sep;276(3):201-14
references.pmid: 24605849
references.citation: Genome Res. 2011 Jun;21(6):974-84
references.pmid: 21324876