Genome-wide Reconstruction of Complex Structural Variants Using Read Clouds

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2017 Jul 18

PMID 28714986

Citations 69

Authors

Noah Spies

Ziming Weng

Alex Bishara

Jennifer McDaniel

David Catoe

Justin M Zook

Marc Salit

Robert B West

Serafim Batzoglou

Arend Sidow

Affiliations

Soon will be listed here.

Abstract

In read cloud approaches, microfluidic partitioning of long genomic DNA fragments and barcoding of shorter fragments derived from these fragments retains long-range information in short sequencing reads. This combination of short reads with long-range information represents a powerful alternative to single-molecule long-read sequencing. We develop Genome-wide Reconstruction of Complex Structural Variants (GROC-SVs) for SV detection and assembly from read cloud data and apply this method to Illumina-sequenced 10x Genomics sarcoma and breast cancer data sets. Compared with short-fragment sequencing, GROC-SVs substantially improves the specificity of breakpoint detection at comparable sensitivity. This approach also performs sequence assembly across multiple breakpoints simultaneously, enabling the reconstruction of events exhibiting remarkable complexity. We show that chromothriptic rearrangements occurred before copy number amplifications, and that rates of single-nucleotide variants and SVs are not correlated. Our results support the use of read cloud approaches to advance the characterization of large and complex structural variation.

Citing Articles

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References

Oliner J, Kinzler K, Meltzer P, GEORGE D, Vogelstein B . Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992; 358(6381):80-3. DOI: 10.1038/358080a0. View

Tupler R, Maraschio P, Gerardo A, Mainieri R, Lanzi G, TIEPOLO L . A complex chromosome rearrangement with 10 breakpoints: tentative assignment of the locus for Williams syndrome to 4q33----q35.1. J Med Genet. 1992; 29(4):253-5. PMC: 1015926. DOI: 10.1136/jmg.29.4.253. View

Garsed D, Marshall O, Corbin V, Hsu A, Stefano L, Schroder J . The architecture and evolution of cancer neochromosomes. Cancer Cell. 2014; 26(5):653-67. DOI: 10.1016/j.ccell.2014.09.010. View

Gao R, Davis A, McDonald T, Sei E, Shi X, Wang Y . Punctuated copy number evolution and clonal stasis in triple-negative breast cancer. Nat Genet. 2016; 48(10):1119-30. PMC: 5042845. DOI: 10.1038/ng.3641. View

Chiang C, Jacobsen J, Ernst C, Hanscom C, Heilbut A, Blumenthal I . Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat Genet. 2012; 44(4):390-7, S1. PMC: 3340016. DOI: 10.1038/ng.2202. View

Weng Z, Spies N, Zhu S, Newburger D, Kashef-Haghighi D, Batzoglou S . Cell-lineage heterogeneity and driver mutation recurrence in pre-invasive breast neoplasia. Genome Med. 2015; 7(1):28. PMC: 4410742. DOI: 10.1186/s13073-015-0146-2. View

Stephens P, Greenman C, Fu B, Yang F, Bignell G, Mudie L . Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011; 144(1):27-40. PMC: 3065307. DOI: 10.1016/j.cell.2010.11.055. View

Bishara A, Liu Y, Weng Z, Kashef-Haghighi D, Newburger D, West R . Read clouds uncover variation in complex regions of the human genome. Genome Res. 2015; 25(10):1570-80. PMC: 4579342. DOI: 10.1101/gr.191189.115. View

Peng Y, Leung H, Yiu S, Chin F . IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth. Bioinformatics. 2012; 28(11):1420-8. DOI: 10.1093/bioinformatics/bts174. View

10.

Yang L, Luquette L, Gehlenborg N, Xi R, Haseley P, Hsieh C . Diverse mechanisms of somatic structural variations in human cancer genomes. Cell. 2013; 153(4):919-29. PMC: 3704973. DOI: 10.1016/j.cell.2013.04.010. View

11.

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

12.

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

13.

Newburger D, Kashef-Haghighi D, Weng Z, Salari R, Sweeney R, Brunner A . Genome evolution during progression to breast cancer. Genome Res. 2013; 23(7):1097-108. PMC: 3698503. DOI: 10.1101/gr.151670.112. View

14.

Peters B, Kermani B, Sparks A, Alferov O, Hong P, Alexeev A . Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells. Nature. 2012; 487(7406):190-5. PMC: 3397394. DOI: 10.1038/nature11236. View

15.

Amini S, Pushkarev D, Christiansen L, Kostem E, Royce T, Turk C . Haplotype-resolved whole-genome sequencing by contiguity-preserving transposition and combinatorial indexing. Nat Genet. 2014; 46(12):1343-9. PMC: 4409979. DOI: 10.1038/ng.3119. View

16.

Sudmant P, Rausch T, Gardner E, Handsaker R, Abyzov A, Huddleston J . An integrated map of structural variation in 2,504 human genomes. Nature. 2015; 526(7571):75-81. PMC: 4617611. DOI: 10.1038/nature15394. View

17.

Baca S, Prandi D, Lawrence M, Mosquera J, Romanel A, Drier Y . Punctuated evolution of prostate cancer genomes. Cell. 2013; 153(3):666-77. PMC: 3690918. DOI: 10.1016/j.cell.2013.03.021. View

18.

Greenman C, Pleasance E, Newman S, Yang F, Fu B, Nik-Zainal S . Estimation of rearrangement phylogeny for cancer genomes. Genome Res. 2011; 22(2):346-61. PMC: 3266042. DOI: 10.1101/gr.118414.110. View

19.

Weischenfeldt J, Symmons O, Spitz F, Korbel J . Phenotypic impact of genomic structural variation: insights from and for human disease. Nat Rev Genet. 2013; 14(2):125-38. DOI: 10.1038/nrg3373. View

20.

Quinlan A, Hall I . Characterizing complex structural variation in germline and somatic genomes. Trends Genet. 2011; 28(1):43-53. PMC: 3249479. DOI: 10.1016/j.tig.2011.10.002. View