title: Systematic comparison of variant calling pipelines using gold standard personal exome variants.
abstract: 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.
authors.affiliation: Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, TX 78712, USA.|Department of Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Eiru
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: Lee
authors.affiliation: Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, TX 78712, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Marcotte
mesh_terms: D001483:Base Sequence; D059472:Exome / Q000235:genetics*; D014644:Genetic Variation; D060005:Genotyping Techniques / Q000379:methods* / Q000592:standards*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012015:Reference Standards