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

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.comSupplementary information: Supplementary data are available at Bioinformatics online.

LongISLND: in silico sequencing of lengthy and noisy datatypes

“…We demonstrated downstream processing of 10-to15-pass of high-error circular sequenced reads (Eid et al , 2009) with PacBio’s latest CCS2 consensus builder, whose output is evaluated to have >99% mappability and Q30 median accuracy. We also demonstrated the VarSim (Mu et al , 2014) evaluation of several off-the-shelf variant calling pipelines, some of which require PacBio-specific data. Supplementary Table S5 also demonstrates significant difficulties in detecting heterozygous variants with P5C3 chemistry.…”

“…The implementation is polymorphic with respect to output file formats. We train our software for multiple PacBio chemistries, instantiate output for multiple file formats, then demonstrate its utility by VarSim (Mu et al , 2014) evaluation of PacBio’s latest CCS2 consensus builder (https://github.com/PacificBiosciences/pbccs) and of various germline and somatic variant callers for PacBio reads.…”

Simulating Next-Generation Sequencing Datasets from Empirical Mutation and Sequencing Models

“…In this regard NEAT could be easily confused with VarSim [10], itself a powerful computational framework with similar functions. However, VarSim is a wrapper around other simulators, and thus inherits all their features and limitations.…”

“…The list of existing simulators compared against are those most often used, according to number of paper citations: ART, CureSim, dwgsim [7], GemSim (including the the targeted sequencing functionality of Wessim [8]), Mason [9], pIRS, and SInC [6]. VarSim [10] is not explicitly listed as it is a wrapper around DWGSIM and ART.…”

A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data

“…Therefore, it is important to identify significant somatic mutations from these variants. Several tools have been developed to do this task for the analysis of cancer WES data, including SomaticSniper [50], MuTect [35], VarSim [51], and SomVarIUS [52]. …”