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Sci Rep. 2017 Sep 8;7(1):10963. doi: 10.1038/s41598-017-10826-9.

Direct comparison of performance of single nucleotide variant calling in human genome with alignment-based and assembly-based approaches.

Author information

1
National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR RD, Jefferson, AR, 72079, USA.
2
National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR RD, Jefferson, AR, 72079, USA. wenming.xiao@fda.hhs.gov.

Abstract

Complementary to reference-based variant detection, recent studies revealed that many novel variants could be detected with de novo assembled genomes. To evaluate the effect of reads coverage and the accuracy of assembly-based variant calling, we simulated short reads containing more than 3 million of single nucleotide variants (SNVs) from the whole human genome and compared the efficiency of SNV calling between the assembly-based and alignment-based calling approaches. We assessed the quality of the assembled contig and found that a minimum of 30X coverage of short reads was needed to ensure reliable SNV calling and to generate assembled contigs with a good coverage of genome and genes. In addition, we observed that the assembly-based approach had a much lower recall rate and precision comparing to the alignment-based approach that would recover 99% of imputed SNVs. We observed similar results with experimental reads for NA24385, an individual whose germline variants were well characterized. Although there are additional values for SNVs detection, the assembly-based approach would have great risk of false discovery of novel SNVs. Further improvement of de novo assembly algorithms are needed in order to warrant a good completeness of genome with haplotype resolved and high fidelity of assembled sequences.

PMID:
28887485
PMCID:
PMC5591230
DOI:
10.1038/s41598-017-10826-9
[Indexed for MEDLINE]
Free PMC Article

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