부산대학교 도서관

Background: De novo mutations (DNMs) are associated with neurodevelopmental and congenital diseases, and their detection can contribute to understanding disease pathogenicity. However, accurate detection is challenging because of their small number relative to the genome-wide false positives in next generation sequencing (NGS) data. Software such as DeNovoGear and TrioDeNovo have been developed to detect DNMs, but at good sensitivity they still produce many false positive calls. Results: To address this challenge, we develop HAPDeNovo, a program that leverages phasing information from linked read sequencing, to remove false positive DNMs from candidate lists generated by DNM-detection tools. Short reads from each phasing block are allocated to each of the two haplotypes followed by generating a haploid genotype for each putative DNM. HAPDeNovo removes variants that are called as heterozygous in one of the haplotypes because they are almost certainly false positives. Our experiments on 10X Chromium linked read sequencing trio data reveal that HAPDeNovo eliminates 80 to 99% of false positives regardless of how large the candidate DNM set is. Conclusions: HAPDeNovo leverages the haplotype information from linked read sequencing to remove spurious false positive DNMs effectively, and it increases accuracy of DNM detection dramatically without sacrificing sensitivity. [ABSTRACT FROM AUTHOR]