De novo reconstruction of microbial haplotypes by integrating statistical and physical linkage
Morrissy, A. Sorana
Sycuro, Laura K.
Jeffares, Daniel C.
Permanent link to this recordhttp://hdl.handle.net/10754/662468
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AbstractAbstractDNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or ‘haplotypes’. However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools in the above four fields, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of HIV previously unobserved in single position-based analysis.
CitationCao, C., He, J., Mak, L., Perera, D., Kwok, D., Wang, J., … Long, Q. (2020). De novo reconstruction of microbial haplotypes by integrating statistical and physical linkage. doi:10.1101/2020.03.29.014704
SponsorsQ.L. is supported by an NSERC Discovery Grant (RGPIN-2017-04860), a 540 Canada Foundation for Innovation JELF grant (36605), and an ACHRI Startup grant. C.C., 541 M.L. and L.M. are supported by ACHRI scholarship. L.M. is supported by a QEII award. G.Y. is 542 supported by an NSERC Discovery Grant (RGPIN/04246-2018)
PublisherCold Spring Harbor Laboratory