Performance assessment of variant calling pipelines using human whole exome sequencing and simulated data

Manojkumar Kumaran,Umadevi Subramanian,Bharanidharan Devarajan

doi:10.1186/s12859-019-2928-9

Manojkumar Kumaran, Umadevi Subramanian + Show 1 more

Open Access

https://doi.org/10.1186/s12859-019-2928-9

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Journal: BMC Bioinformatics	Publication Date: Jun 17, 2019
Citations: 48	License type: open-access

Affiliation: SASTRA University

Abstract

BackgroundWhole exome sequencing (WES) is a cost-effective method that identifies clinical variants but it demands accurate variant caller tools. Currently available tools have variable accuracy in predicting specific clinical variants. But it may be possible to find the best combination of aligner-variant caller tools for detecting accurate single nucleotide variants (SNVs) and small insertion and deletion (InDels) separately. Moreover, many important aspects of InDel detection are overlooked while comparing the performance of tools, particularly its base pair length.ResultsWe assessed the performance of variant calling pipelines using the combinations of four variant callers and five aligners on human NA12878 and simulated exome data. We used high confidence variant calls from Genome in a Bottle (GiaB) consortium for validation, and GRCh37 and GRCh38 as the human reference genome. Based on the performance metrics, both BWA and Novoalign aligners performed better with DeepVariant and SAMtools callers for detecting SNVs, and with DeepVariant and GATK for InDels. Furthermore, we obtained similar results on human NA24385 and NA24631 exome data from GiaB.ConclusionIn this study, DeepVariant with BWA and Novoalign performed best for detecting accurate SNVs and InDels. The accuracy of variant calling was improved by merging the top performing pipelines. The results of our study provide useful recommendations for analysis of WES data in clinical genomics.

Highlights

Whole exome sequencing (WES) is a cost-effective method that identifies clinical variants but it demands accurate variant caller tools
In order to assess the performance of variant calling pipelines in terms of their capacity to accurately detect single nucleotide variants (SNVs) and Insertions and Deletions (InDels) from WES datasets, we developed 20 pipelines with the combinations of four variant caller and five aligner tools
The results were validated with high confidence truth set from Genome in a Bottle (GiaB) for both the human GRCh37 and GRCh38 reference and compared the results with gold standard truth variants provided by GiaB consortium

Summary

Introduction

Whole exome sequencing (WES) is a cost-effective method that identifies clinical variants but it demands accurate variant caller tools. It may be possible to find the best combination of aligner-variant caller tools for detecting accurate single nucleotide variants (SNVs) and small insertion and deletion (InDels) separately. Whole genome sequencing (WGS) and Whole exome sequencing (WES) methods are applied in clinical settings for detecting patient’s genomic variants and etiology of the disease. No single pipeline with the combination of aligner and variant caller has demonstrated superiority in detecting all the variants. It is essential to evaluate variant calling pipelines with the optimal combination of Kumaran et al BMC Bioinformatics (2019) 20:342 aligners and variant callers that may produce accurate variant calls including single nucleotide variants (SNVs) and small insertion and deletion (InDels)

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Results

Conclusion