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

John C Mu; Marghoob Mohiyuddin; Jian Li; Narges Bani Asadi; Mark B Gerstein; Alexej Abyzov; Wing H Wong; Hugo Y K Lam

doi:10.1093/bioinformatics/btu828

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

Bioinformatics. 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.

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.

Publication types

Research Support, N.I.H., Extramural
Validation Study

MeSH terms

Computer Simulation
Genetic Variation*
Genomics
High-Throughput Nucleotide Sequencing / methods*
Humans
Mutation
Neoplasms / genetics
Sequence Alignment
Software*

Abstract

Publication types

MeSH terms

Grants and funding