PSCC: Sensitive and Reliable Population-scale Copy Number Variation Detection Method Based on Low Coverage Sequencing

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 28

PMID 24465483

Citations 17

Authors

Xuchao Li

Shengpei Chen

WeiWei Xie

Ida Vogel

Kwong Wai Choy

Fang Chen

Rikke Christensen

Chunlei Zhang

Huijuan Ge

Haojun Jiang

Chang Yu

Fang Huang

Wei Wang

Hui Jiang

Xiuqing Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Copy number variations (CNVs) represent an important type of genetic variation that deeply impact phenotypic polymorphisms and human diseases. The advent of high-throughput sequencing technologies provides an opportunity to revolutionize the discovery of CNVs and to explore their relationship with diseases. However, most of the existing methods depend on sequencing depth and show instability with low sequence coverage. In this study, using low coverage whole-genome sequencing (LCS) we have developed an effective population-scale CNV calling (PSCC) method.

Methodology/principal Findings: In our novel method, two-step correction was used to remove biases caused by local GC content and complex genomic characteristics. We chose a binary segmentation method to locate CNV segments and designed combined statistics tests to ensure the stable performance of the false positive control. The simulation data showed that our PSCC method could achieve 99.7%/100% and 98.6%/100% sensitivity and specificity for over 300 kb CNV calling in the condition of LCS (∼2×) and ultra LCS (∼0.2×), respectively. Finally, we applied this novel method to analyze 34 clinical samples with an average of 2× LCS. In the final results, all the 31 pathogenic CNVs identified by aCGH were successfully detected. In addition, the performance comparison revealed that our method had significant advantages over existing methods using ultra LCS.

Conclusions/significance: Our study showed that PSCC can sensitively and reliably detect CNVs using low coverage or even ultra-low coverage data through population-scale sequencing.

Citing Articles

Retrospective study revealed integration of CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities.

Ge Y, Chen J, Huang Y, Shao D, Wang W, Cai M Front Genet. 2024; 15:1387724.

PMID: 38846960 PMC: 11153659. DOI: 10.3389/fgene.2024.1387724.

Accuracy and depth evaluation of clinical low pass genome sequencing in the detection of mosaic aneuploidies and CNVs.

Liu Y, Hao S, Guo X, Fan L, Qiao Z, Wang Y BMC Med Genomics. 2023; 16(1):294.

PMID: 37978521 PMC: 10656965. DOI: 10.1186/s12920-023-01703-8.

Evaluation and Analysis of Absence of Homozygosity (AOH) Using Chromosome Analysis by Medium Coverage Whole Genome Sequencing (CMA-seq) in Prenatal Diagnosis.

Lu Y, Jiang Y, Zhou X, Hao N, Lu G, Guo X Diagnostics (Basel). 2023; 13(3).

PMID: 36766665 PMC: 9914714. DOI: 10.3390/diagnostics13030560.

Clinical and Genetic Characteristics of a Cohort with Distal Vaginal Atresia.

Kang J, Zhou Q, Chen N, Liu Z, Zhang Y, Sun J Int J Mol Sci. 2022; 23(21).

PMID: 36361644 PMC: 9655474. DOI: 10.3390/ijms232112853.

Genetic Diagnostic Yield and Novel Causal Genes of Congenital Heart Disease.

Tan M, Wang X, Liu H, Peng X, Yang Y, Yu H Front Genet. 2022; 13:941364.

PMID: 35910219 PMC: 9326225. DOI: 10.3389/fgene.2022.941364.

References

Magi A, Tattini L, Pippucci T, Torricelli F, Benelli M . Read count approach for DNA copy number variants detection. Bioinformatics. 2011; 28(4):470-8. DOI: 10.1093/bioinformatics/btr707. View

Yoon S, Xuan Z, Makarov V, Ye K, Sebat J . Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Res. 2009; 19(9):1586-92. PMC: 2752127. DOI: 10.1101/gr.092981.109. View

Magi A, Benelli M, Marseglia G, Nannetti G, Scordo M, Torricelli F . A shifting level model algorithm that identifies aberrations in array-CGH data. Biostatistics. 2009; 11(2):265-80. DOI: 10.1093/biostatistics/kxp051. View

Medvedev P, Stanciu M, Brudno M . Computational methods for discovering structural variation with next-generation sequencing. Nat Methods. 2009; 6(11 Suppl):S13-20. DOI: 10.1038/nmeth.1374. View

Ivakhno S, Royce T, Cox A, Evers D, Cheetham R, Tavare S . CNAseg--a novel framework for identification of copy number changes in cancer from second-generation sequencing data. Bioinformatics. 2010; 26(24):3051-8. DOI: 10.1093/bioinformatics/btq587. View

de Smith A, Tsalenko A, Sampas N, Scheffer A, Yamada N, Tsang P . Array CGH analysis of copy number variation identifies 1284 new genes variant in healthy white males: implications for association studies of complex diseases. Hum Mol Genet. 2007; 16(23):2783-94. DOI: 10.1093/hmg/ddm208. View

Ptacek T, Li X, Kelley J, Edberg J . Copy number variants in genetic susceptibility and severity of systemic lupus erythematosus. Cytogenet Genome Res. 2009; 123(1-4):142-7. PMC: 2826785. DOI: 10.1159/000184701. View

Ballantyne K, van Oorschot R, Muharam I, Daal A, Mitchell R . Decreasing amplification bias associated with multiple displacement amplification and short tandem repeat genotyping. Anal Biochem. 2007; 368(2):222-9. DOI: 10.1016/j.ab.2007.05.017. View

Jakobsson M, Scholz S, Scheet P, Gibbs J, Vanliere J, Fung H . Genotype, haplotype and copy-number variation in worldwide human populations. Nature. 2008; 451(7181):998-1003. DOI: 10.1038/nature06742. View

10.

Hastings P, Lupski J, Rosenberg S, Ira G . Mechanisms of change in gene copy number. Nat Rev Genet. 2009; 10(8):551-64. PMC: 2864001. DOI: 10.1038/nrg2593. View

11.

Kusenda M, Sebat J . The role of rare structural variants in the genetics of autism spectrum disorders. Cytogenet Genome Res. 2009; 123(1-4):36-43. PMC: 2920182. DOI: 10.1159/000184690. View

12.

Kim T, Luquette L, Xi R, Park P . rSW-seq: algorithm for detection of copy number alterations in deep sequencing data. BMC Bioinformatics. 2010; 11:432. PMC: 2939611. DOI: 10.1186/1471-2105-11-432. View

13.

Campbell P, Stephens P, Pleasance E, OMeara S, Li H, Santarius T . Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet. 2008; 40(6):722-9. PMC: 2705838. DOI: 10.1038/ng.128. View

14.

Xie C, Tammi M . CNV-seq, a new method to detect copy number variation using high-throughput sequencing. BMC Bioinformatics. 2009; 10:80. PMC: 2667514. DOI: 10.1186/1471-2105-10-80. View

15.

Shen Y, Wu B . Designing a simple multiplex ligation-dependent probe amplification (MLPA) assay for rapid detection of copy number variants in the genome. J Genet Genomics. 2009; 36(4):257-65. DOI: 10.1016/S1673-8527(08)60113-7. View

16.

Klopocki E, Lohan S, Brancati F, Koll R, Brehm A, Seemann P . Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis. Am J Hum Genet. 2010; 88(1):70-5. PMC: 3014361. DOI: 10.1016/j.ajhg.2010.11.006. View

17.

Chiang D, Getz G, Jaffe D, OKelly M, Zhao X, Carter S . High-resolution mapping of copy-number alterations with massively parallel sequencing. Nat Methods. 2008; 6(1):99-103. PMC: 2630795. DOI: 10.1038/nmeth.1276. View

18.

Conrad D, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y . Origins and functional impact of copy number variation in the human genome. Nature. 2009; 464(7289):704-12. PMC: 3330748. DOI: 10.1038/nature08516. View

19.

Takahashi N, Satoh Y, Kodaira M, Katayama H . Large-scale copy number variants (CNVs) detected in different ethnic human populations. Cytogenet Genome Res. 2009; 123(1-4):224-33. DOI: 10.1159/000184712. View

20.

Dohm J, Lottaz C, Borodina T, Himmelbauer H . Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res. 2008; 36(16):e105. PMC: 2532726. DOI: 10.1093/nar/gkn425. View