Systematic comparison of variant calling pipelines using gold standard personal exome variants

The success of clinical genomics using next generation sequencing (NGS) requires the accurate and consistent identification of personal genome variants. Assorted variant calling methods have been developed, which show low concordance between their calls. Hence, a systematic comparison of the variant...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2015-12, Vol.5 (1), p.17875-17875, Article 17875
Main Authors: Hwang, Sohyun, Kim, Eiru, Lee, Insuk, Marcotte, Edward M
Format: Article
Language:English
Subjects:
Base Sequence
Exome - genetics
Genetic Variation
Genomes
Genomics
Genotyping
Genotyping Techniques - methods
Genotyping Techniques - standards
High-Throughput Nucleotide Sequencing
Humans
Pipelines
Polymorphism, Single Nucleotide - genetics
Reference Standards
Single-nucleotide polymorphism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The success of clinical genomics using next generation sequencing (NGS) requires the accurate and consistent identification of personal genome variants. Assorted variant calling methods have been developed, which show low concordance between their calls. Hence, a systematic comparison of the variant callers could give important guidance to NGS-based clinical genomics. Recently, a set of high-confident variant calls for one individual (NA12878) has been published by the Genome in a Bottle (GIAB) consortium, enabling performance benchmarking of different variant calling pipelines. Based on the gold standard reference variant calls from GIAB, we compared the performance of thirteen variant calling pipelines, testing combinations of three read aligners--BWA-MEM, Bowtie2, and Novoalign--and four variant callers--Genome Analysis Tool Kit HaplotypeCaller (GATK-HC), Samtools mpileup, Freebayes and Ion Proton Variant Caller (TVC), for twelve data sets for the NA12878 genome sequenced by different platforms including Illumina2000, Illumina2500, and Ion Proton, with various exome capture systems and exome coverage. We observed different biases toward specific types of SNP genotyping errors by the different variant callers. The results of our study provide useful guidelines for reliable variant identification from deep sequencing of personal genomes.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep17875