Towards Better Understanding of Artifacts in Variant Calling from High-Coverage Samples
arXiv:1404.0929 · doi:10.1093/bioinformatics/btu356
Abstract
Motivation: Whole-genome high-coverage sequencing has been widely used for personal and cancer genomics as well as in various research areas. However, in the lack of an unbiased whole-genome truth set, the global error rate of variant calls and the leading causal artifacts still remain unclear even given the great efforts in the evaluation of variant calling methods. Results: We made ten SNP and INDEL call sets with two read mappers and five variant callers, both on a haploid human genome and a diploid genome at a similar coverage. By investigating false heterozygous calls in the haploid genome, we identified the erroneous realignment in low-complexity regions and the incomplete reference genome with respect to the sample as the two major sources of errors, which press for continued improvements in these two areas. We estimated that the error rate of raw genotype calls is as high as 1 in 10-15kb, but the error rate of post-filtered calls is reduced to 1 in 100-200kb without significant compromise on the sensitivity. Availability: BWA-MEM alignment: http://bit.ly/1g8XqRt; Scripts: https://github.com/lh3/varcmp; Additional data: https://figshare.com/articles/Towards_better_understanding_of_artifacts_in_variating_calling_from_high_coverage_samples/981073
Published version
References in corpus (4)
- A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data
- Haplotype-based variant detection from short-read sequencing
- Exploring single-sample SNP and INDEL calling with whole-genome de novo assembly
- Mapping to a Reference Genome Structure
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- Whole genome sequencing identifies putative associations between genomic polymorphisms and clinical response to the antiepileptic drug levetiracetam