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dc.contributor.authorCao, Chen
dc.contributor.authorHe, Jingni
dc.contributor.authorMak, Lauren
dc.contributor.authorPerera, Deshan
dc.contributor.authorKwok, Devin
dc.contributor.authorWang, Jia
dc.contributor.authorLi, Minghao
dc.contributor.authorMourier, Tobias
dc.contributor.authorGavriliuc, Stefan
dc.contributor.authorGreenberg, Matthew
dc.contributor.authorMorrissy, A. Sorana
dc.contributor.authorSycuro, Laura K.
dc.contributor.authorYANG, GUANG
dc.contributor.authorJeffares, Daniel C.
dc.contributor.authorLong, Quan
dc.date.accessioned2020-04-09T10:07:03Z
dc.date.available2020-04-09T10:07:03Z
dc.date.issued2020-03-30
dc.identifier.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
dc.identifier.doi10.1101/2020.03.29.014704
dc.identifier.urihttp://hdl.handle.net/10754/662468
dc.description.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.
dc.description.sponsorshipQ.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)
dc.publisherCold Spring Harbor Laboratory
dc.relation.urlhttp://biorxiv.org/lookup/doi/10.1101/2020.03.29.014704
dc.rightsArchived with thanks to Cold Spring Harbor Laboratory
dc.titleDe novo reconstruction of microbial haplotypes by integrating statistical and physical linkage
dc.typePreprint
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.eprint.versionPre-print
dc.contributor.institutionDepartment of Biochemistry & Molecular Biology, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada.
dc.contributor.institutionCurrent address: Tri-Institutional Computational Biology & Medicine Program, Weill Cornell Medicine of Cornell University, NY, USA.
dc.contributor.institutionDepartment of Mathematics & Statistics, University of Calgary, Calgary, Canada.
dc.contributor.institutionElectrical and Computer Engineering, Illinois Institute of Technology, Chicago, USA.
dc.contributor.institutionDepartment of Microbiology, Immunology, and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Canada.
dc.contributor.institutionDepartment of Medical Genetics, University of Calgary, Calgary, Canada.
dc.contributor.institutionYork Biomedical Research Institute, Department of Biology, University of York. Wentworth Way, York, United Kingdom.
dc.contributor.institutionHotchkiss Brain Institute, O’Brien Institute for Public Health, University of Calgary, Calgary, Canada
kaust.personMourier, Tobias
refterms.dateFOA2020-04-09T10:09:40Z


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