VarSim: a high-fidelity simulation and validation framework for high-throughput genome sequencing with cancer applications

John C Mu¹, Marghoob Mohiyuddin², Jian Li², Narges Bani Asadi², Mark B Gerstein², Alexej Abyzov², Wing H Wong¹, Hugo Y K Lam²

Affiliations

¹ Department of Electrical Engineering, Stanford University, Stanford, CA 94035, USA, Department of Bioinformatics, Bina Technologies, Redwood City, CA 94065, USA, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA, Mayo Clinics, Department of Health Sciences Research, Rochester, MN 55902, USA, Department of Statistics, Stanford University, Stanford, CA 94035, USA and Department of Health Research and Policy, Stanford University, Stanford, CA 94035, USA Department of Electrical Engineering, Stanford University, Stanford, CA 94035, USA, Department of Bioinformatics, Bina Technologies, Redwood City, CA 94065, USA, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA, Mayo Clinics, Department of Health Sciences Research, Rochester, MN 55902, USA, Department of Statistics, Stanford University, Stanford, CA 94035, USA and Department of Health Research and Policy, Stanford University, Stanford, CA 94035, USA.
² Department of Electrical Engineering, Stanford University, Stanford, CA 94035, USA, Department of Bioinformatics, Bina Technologies, Redwood City, CA 94065, USA, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA, Mayo Clinics, Department of Health Sciences Research, Rochester, MN 55902, USA, Department of Statistics, Stanford University, Stanford, CA 94035, USA and Department of Health Research and Policy, Stanford University, Stanford, CA 94035, USA.

PMID: 25524895
PMCID: PMC4410653
DOI: 10.1093/bioinformatics/btu828

VarSim: a high-fidelity simulation and validation framework for high-throughput genome sequencing with cancer applications

John C Mu et al. Bioinformatics. 2015.

. 2015 May 1;31(9):1469-71.

doi: 10.1093/bioinformatics/btu828. Epub 2014 Dec 17.

Authors

John C Mu¹, Marghoob Mohiyuddin², Jian Li², Narges Bani Asadi², Mark B Gerstein², Alexej Abyzov², Wing H Wong¹, Hugo Y K Lam²

Affiliations

¹ Department of Electrical Engineering, Stanford University, Stanford, CA 94035, USA, Department of Bioinformatics, Bina Technologies, Redwood City, CA 94065, USA, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA, Mayo Clinics, Department of Health Sciences Research, Rochester, MN 55902, USA, Department of Statistics, Stanford University, Stanford, CA 94035, USA and Department of Health Research and Policy, Stanford University, Stanford, CA 94035, USA Department of Electrical Engineering, Stanford University, Stanford, CA 94035, USA, Department of Bioinformatics, Bina Technologies, Redwood City, CA 94065, USA, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA, Mayo Clinics, Department of Health Sciences Research, Rochester, MN 55902, USA, Department of Statistics, Stanford University, Stanford, CA 94035, USA and Department of Health Research and Policy, Stanford University, Stanford, CA 94035, USA.
² Department of Electrical Engineering, Stanford University, Stanford, CA 94035, USA, Department of Bioinformatics, Bina Technologies, Redwood City, CA 94065, USA, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA, Mayo Clinics, Department of Health Sciences Research, Rochester, MN 55902, USA, Department of Statistics, Stanford University, Stanford, CA 94035, USA and Department of Health Research and Policy, Stanford University, Stanford, CA 94035, USA.

PMID: 25524895
PMCID: PMC4410653
DOI: 10.1093/bioinformatics/btu828

Abstract

Summary: VarSim is a framework for assessing alignment and variant calling accuracy in high-throughput genome sequencing through simulation or real data. In contrast to simulating a random mutation spectrum, it synthesizes diploid genomes with germline and somatic mutations based on a realistic model. This model leverages information such as previously reported mutations to make the synthetic genomes biologically relevant. VarSim simulates and validates a wide range of variants, including single nucleotide variants, small indels and large structural variants. It is an automated, comprehensive compute framework supporting parallel computation and multiple read simulators. Furthermore, we developed a novel map data structure to validate read alignments, a strategy to compare variants binned in size ranges and a lightweight, interactive, graphical report to visualize validation results with detailed statistics. Thus far, it is the most comprehensive validation tool for secondary analysis in next generation sequencing.

Availability and implementation: Code in Java and Python along with instructions to download the reads and variants is at http://bioinform.github.io/varsim.

Contact: rd@bina.com

Supplementary information: Supplementary data are available at Bioinformatics online.

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Figures

**Fig. 1.**
VarSim simulation and validation workflow. The germline workflow can be run with or without the somatic workflow

**Fig. 2.**
Validation results for some popular secondary analysis tools

See this image and copyright information in PMC

References

1. Abyzov A., et al. . (2011) Cnvnator: an approach to discover, genotype, and characterize typical and atypical cnvs from family and population genome sequencing. Genome Res. , 21, 974–984. - PMC - PubMed
1. Bartenhagen C., Dugas M. (2013) RSVSim: an R/Bioconductor package for the simulation of structural variations. Bioinformatics , 29, 1679–1681. - PubMed
1. Chen K., et al. (2009) BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat. Methods , 6, 677–681. - PMC - PubMed
1. Cibulskis K., et al. (2013) Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. , 31, 213–219. - PMC - PubMed
1. Forbes S.A., et al. (2014) COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res, 43, D805–D811. - PMC - PubMed

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VarSim: a high-fidelity simulation and validation framework for high-throughput genome sequencing with cancer applications

Affiliations

VarSim: a high-fidelity simulation and validation framework for high-throughput genome sequencing with cancer applications

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous