NpInv: Accurate Detection and Genotyping of Inversions Using Long Read Sub-alignment

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2018 Jul 14

PMID 30001702

Citations 20

Authors

Haojing Shao

Devika Ganesamoorthy

Tania Duarte

Minh Duc Cao

Clive J Hoggart

Lachlan J M Coin

Affiliations

Soon will be listed here.

Abstract

Background: Detection of genomic inversions remains challenging. Many existing methods primarily target inzversions with a non repetitive breakpoint, leaving inverted repeat (IR) mediated non-allelic homologous recombination (NAHR) inversions largely unexplored.

Result: We present npInv, a novel tool specifically for detecting and genotyping NAHR inversion using long read sub-alignment of long read sequencing data. We benchmark npInv with other tools in both simulation and real data. We use npInv to generate a whole-genome inversion map for NA12878 consisting of 30 NAHR inversions (of which 15 are novel), including all previously known NAHR mediated inversions in NA12878 with flanking IR less than 7kb. Our genotyping accuracy on this dataset was 94%. We used PCR to confirm the presence of two of these novel inversions. We show that there is a near linear relationship between the length of flanking IR and the minimum inversion size, without inverted repeats.

Conclusion: The application of npInv shows high accuracy in both simulation and real data. The results give deeper insight into understanding inversion.

Citing Articles

Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast.

Cautereels C, Smets J, Bircham P, De Ruysscher D, Zimmermann A, De Rijk P Nat Commun. 2024; 15(1):1112.

PMID: 38326309 PMC: 10850122. DOI: 10.1038/s41467-024-44997-7.

Mitochondrial GpC and CpG DNA Hypermethylation Cause Metabolic Stress-Induced Mitophagy and Cholestophagy.

Theys C, Ibrahim J, Mateiu L, Mposhi A, Garcia-Pupo L, De Pooter T Int J Mol Sci. 2023; 24(22).

PMID: 38003603 PMC: 10671279. DOI: 10.3390/ijms242216412.

A survey of algorithms for the detection of genomic structural variants from long-read sequencing data.

Ahsan M, Liu Q, Perdomo J, Fang L, Wang K Nat Methods. 2023; 20(8):1143-1158.

PMID: 37386186 PMC: 11208083. DOI: 10.1038/s41592-023-01932-w.

A Cas3-base editing tool for targetable in vivo mutagenesis.

Zimmermann A, Prieto-Vivas J, Cautereels C, Gorkovskiy A, Steensels J, Van de Peer Y Nat Commun. 2023; 14(1):3389.

PMID: 37296137 PMC: 10256805. DOI: 10.1038/s41467-023-39087-z.

Independent Evolution of Sex Chromosomes and Male Pregnancy-Related Genes in Two Seahorse Species.

Long X, Charlesworth D, Qi J, Wu R, Chen M, Wang Z Mol Biol Evol. 2022; 40(1).

PMID: 36578180 PMC: 9851323. DOI: 10.1093/molbev/msac279.

References

Pang A, MacDonald J, Pinto D, Wei J, Rafiq M, Conrad D . Towards a comprehensive structural variation map of an individual human genome. Genome Biol. 2010; 11(5):R52. PMC: 2898065. DOI: 10.1186/gb-2010-11-5-r52. View

Zhang F, Khajavi M, Connolly A, Towne C, Batish S, Lupski J . The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans. Nat Genet. 2009; 41(7):849-53. PMC: 4461229. DOI: 10.1038/ng.399. View

Richter D, Ott F, Auch A, Schmid R, Huson D . MetaSim: a sequencing simulator for genomics and metagenomics. PLoS One. 2008; 3(10):e3373. PMC: 2556396. DOI: 10.1371/journal.pone.0003373. View

Feuk L, Carson A, Scherer S . Structural variation in the human genome. Nat Rev Genet. 2006; 7(2):85-97. DOI: 10.1038/nrg1767. View

Osborne L, Li M, Pober B, Chitayat D, Bodurtha J, Mandel A . A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome. Nat Genet. 2001; 29(3):321-5. PMC: 2889916. DOI: 10.1038/ng753. View

Warburton P, Giordano J, Cheung F, Gelfand Y, Benson G . Inverted repeat structure of the human genome: the X-chromosome contains a preponderance of large, highly homologous inverted repeats that contain testes genes. Genome Res. 2004; 14(10A):1861-9. PMC: 524409. DOI: 10.1101/gr.2542904. View

Conway J, Lex A, Gehlenborg N . UpSetR: an R package for the visualization of intersecting sets and their properties. Bioinformatics. 2017; 33(18):2938-2940. PMC: 5870712. DOI: 10.1093/bioinformatics/btx364. View

Gimelli G, Pujana M, Patricelli M, Russo S, Giardino D, Larizza L . Genomic inversions of human chromosome 15q11-q13 in mothers of Angelman syndrome patients with class II (BP2/3) deletions. Hum Mol Genet. 2003; 12(8):849-58. DOI: 10.1093/hmg/ddg101. View

Treangen T, Salzberg S . Repetitive DNA and next-generation sequencing: computational challenges and solutions. Nat Rev Genet. 2011; 13(1):36-46. PMC: 3324860. DOI: 10.1038/nrg3117. View

10.

Kidd J, Cooper G, Donahue W, Hayden H, Sampas N, Graves T . Mapping and sequencing of structural variation from eight human genomes. Nature. 2008; 453(7191):56-64. PMC: 2424287. DOI: 10.1038/nature06862. View

11.

Ahn S, Kim T, Lee S, Kim D, Ghang H, Kim D . The first Korean genome sequence and analysis: full genome sequencing for a socio-ethnic group. Genome Res. 2009; 19(9):1622-9. PMC: 2752128. DOI: 10.1101/gr.092197.109. View

12.

Noe L, Kucherov G . YASS: enhancing the sensitivity of DNA similarity search. Nucleic Acids Res. 2005; 33(Web Server issue):W540-3. PMC: 1160238. DOI: 10.1093/nar/gki478. View

13.

Sedlazeck F, Rescheneder P, Smolka M, Fang H, Nattestad M, von Haeseler A . Accurate detection of complex structural variations using single-molecule sequencing. Nat Methods. 2018; 15(6):461-468. PMC: 5990442. DOI: 10.1038/s41592-018-0001-7. View

14.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N . The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25(16):2078-9. PMC: 2723002. DOI: 10.1093/bioinformatics/btp352. View

15.

Layer R, Chiang C, Quinlan A, Hall I . LUMPY: a probabilistic framework for structural variant discovery. Genome Biol. 2014; 15(6):R84. PMC: 4197822. DOI: 10.1186/gb-2014-15-6-r84. View

16.

Rausch T, Zichner T, Schlattl A, Stutz A, Benes V, Korbel J . DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics. 2012; 28(18):i333-i339. PMC: 3436805. DOI: 10.1093/bioinformatics/bts378. View

17.

Shao H, Bellos E, Yin H, Liu X, Zou J, Li Y . A population model for genotyping indels from next-generation sequence data. Nucleic Acids Res. 2012; 41(3):e46. PMC: 3562001. DOI: 10.1093/nar/gks1143. View

18.

Martinez-Fundichely A, Casillas S, Egea R, Ramia M, Barbadilla A, Pantano L . InvFEST, a database integrating information of polymorphic inversions in the human genome. Nucleic Acids Res. 2013; 42(Database issue):D1027-32. PMC: 3965118. DOI: 10.1093/nar/gkt1122. View

19.

Giglio S, Calvari V, Gregato G, Gimelli G, Camanini S, Giorda R . Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation. Am J Hum Genet. 2002; 71(2):276-85. PMC: 379160. DOI: 10.1086/341610. View

20.

Danecek P, Auton A, Abecasis G, Albers C, Banks E, DePristo M . The variant call format and VCFtools. Bioinformatics. 2011; 27(15):2156-8. PMC: 3137218. DOI: 10.1093/bioinformatics/btr330. View