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Recovery of gene haplotypes from a metagenome

View ORCID ProfileSamuel M. Nicholls, View ORCID ProfileWayne Aubrey, Arwyn Edwards, Kurt de Grave, Sharon Huws, Leander Schietgat, André Soares, View ORCID ProfileChristopher J. Creevey, View ORCID ProfileAmanda Clare
doi: https://doi.org/10.1101/223404
Samuel M. Nicholls
1Department of Computer Science, Aberystwyth University, Aberystwyth, UK
2Department of Computer Science, Katholieke Universiteit Leuven, Leuven, Belgium
3Institute of Biological, Rural and Environmental Sciences, Aberystwyth University, Aberystwyth, UK
6Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK
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  • For correspondence: sam@samnicholls.net
Wayne Aubrey
1Department of Computer Science, Aberystwyth University, Aberystwyth, UK
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Arwyn Edwards
3Institute of Biological, Rural and Environmental Sciences, Aberystwyth University, Aberystwyth, UK
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Kurt de Grave
2Department of Computer Science, Katholieke Universiteit Leuven, Leuven, Belgium
4Flanders Make, Lommel, Belgium
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Sharon Huws
3Institute of Biological, Rural and Environmental Sciences, Aberystwyth University, Aberystwyth, UK
5Institute of Global Food Security, School of Biological Sciences, Queen’s University, Belfast, UK
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Leander Schietgat
2Department of Computer Science, Katholieke Universiteit Leuven, Leuven, Belgium
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André Soares
3Institute of Biological, Rural and Environmental Sciences, Aberystwyth University, Aberystwyth, UK
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Christopher J. Creevey
3Institute of Biological, Rural and Environmental Sciences, Aberystwyth University, Aberystwyth, UK
5Institute of Global Food Security, School of Biological Sciences, Queen’s University, Belfast, UK
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Amanda Clare
1Department of Computer Science, Aberystwyth University, Aberystwyth, UK
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Abstract

Elucidation of population-level diversity of microbiomes is a significant step towards a complete understanding of the evolutionary, ecological and functional importance of microbial communities. Characterizing this diversity requires the recovery of the exact DNA sequence (haplotype) of each gene isoform from every individual present in the community. To address this, we present Hansel and Gretel: a freely-available data structure and algorithm, providing a software package that reconstructs the most likely haplotypes from metagenomes. We demonstrate recovery of haplotypes from short-read Illumina data for a bovine rumen microbiome, and verify our predictions are 100% accurate with long-read PacBio CCS sequencing. We show that Gretel’s haplotypes can be analyzed to determine a significant difference in mutation rates between core and accessory gene families in an ovine rumen microbiome. All tools, documentation and data for evaluation are open source and available via our repository: https://github.com/samstudio8/gretel

Footnotes

  • ↵* The authors wish it to be known that in their opinion, the last two authors should be regarded as joint Last Authors.

  • * Reorganises and dramatically shortens the paper * Replaces the Nanopore-based validation with PacBio sequencing

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 17, 2019.
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Recovery of gene haplotypes from a metagenome
Samuel M. Nicholls, Wayne Aubrey, Arwyn Edwards, Kurt de Grave, Sharon Huws, Leander Schietgat, André Soares, Christopher J. Creevey, Amanda Clare
bioRxiv 223404; doi: https://doi.org/10.1101/223404
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Recovery of gene haplotypes from a metagenome
Samuel M. Nicholls, Wayne Aubrey, Arwyn Edwards, Kurt de Grave, Sharon Huws, Leander Schietgat, André Soares, Christopher J. Creevey, Amanda Clare
bioRxiv 223404; doi: https://doi.org/10.1101/223404

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