Cao, Chen, He, Jingni, Mak, Lauren et al. (12 more authors) (2021) Reconstruction of Microbial Haplotypes by Integration of Statistical and Physical Linkage in Scaffolding. Molecular Biology and Evolution. pp. 2660-2672. ISSN 0737-4038
Abstract
DNA 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 tailored to specific organismal systems, 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 within-patient HIV populations previously unobserved in single position-based analysis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. |
Keywords: | haplotype reconstruction,linkage disequilibrium,regularization,within-host evolution |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) |
Depositing User: | Pure (York) |
Date Deposited: | 12 Mar 2021 16:30 |
Last Modified: | 02 Apr 2025 23:21 |
Published Version: | https://doi.org/10.1093/molbev/msab037 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1093/molbev/msab037 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:172135 |
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Description: Reconstruction of Microbial Haplotypes by Integration of Statistical and Physical Linkage in Scaffolding
Licence: CC-BY 2.5