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MetaPop: A pipeline for macro- and micro-diversity analyses and visualization of microbial and viral metagenome-derived populations

Ann C. Gregory, Kenji Gerhardt, Zhi-Ping Zhong, Benjamin Bolduc, Ben Temperton, Konstantinos T. Konstantinidis, Matthew B. Sullivan
doi: https://doi.org/10.1101/2020.11.01.363960
Ann C. Gregory
1Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA
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Kenji Gerhardt
1Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA
2School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA
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Zhi-Ping Zhong
1Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA
3Byrd Polar and Climate Research Center, The Ohio State University, Columbus, OH, 43210, USA
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Benjamin Bolduc
1Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA
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Ben Temperton
4School of Biosciences, University of Exeter, Exeter, UK
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Konstantinos T. Konstantinidis
2School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA
5School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
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Matthew B. Sullivan
1Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA
6Center of Microbiome Science, The Ohio State University, Columbus, OH 43210, USA
7Department of Civil, Environmental and Geodetic Engineering, The Ohio State University, Columbus, OH 43210, USA
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  • For correspondence: sullivan.948@osu.edu
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Abstract

Background Microbes and their viruses are hidden engines driving Earth’s ecosystems from the oceans and soils to humans and bioreactors. Though gene marker approaches can now be complemented by genome-resolved studies of inter- (macrodiversity) and intra- (microdiversity) population variation, analytical tools to do so remain scattered or under-developed.

Results Here we introduce MetaPop, an open-source bioinformatic pipeline that provides a single interface to analyze and visualize microbial and viral community metagenomes at both the macro- and micro-diversity levels. Macrodiversity estimates include population abundances and α- and β-diversity. Microdiversity calculations include identification of single nucleotide polymorphisms, novel codon-constrained linkage of SNPs, nucleotide diversity (π and θ) and selective pressures (pN/pS and Tajima’s D) within and fixation indices (FST) between populations. MetaPop will also identify genes with distinct codon usage. Following rigorous validation, we applied MetaPop to the gut viromes of autistic children that underwent fecal microbiota transfers and their neurotypical peers. The macrodiversity results confirmed our prior findings for viral populations (microbial shotgun metagenomes were not available), that diversity did not significantly differ between autistic and neurotypical children. However, by also quantifying microdiversity, MetaPop revealed lower average viral nucleotide diversity (π) in autistic children. Analysis of the percentage of genomes detected under positive selection was also lower among autistic children, suggesting that higher viral π in neurotypical children may be beneficial because it allows populations to better ‘bet hedge’ in changing environments. Further, comparisons of microdiversity pre- and post-FMT in the autistic children revealed that the delivery FMT method (oral versus rectal) may influence viral activity and engraftment of microdiverse viral populations, with children who received their FMT rectally having higher microdiversity post-FMT. Overall, these results show that analyses at the macro-level alone can miss important biological differences.

Conclusions These findings suggest that standardized population and genetic variation analyses will be invaluable for maximizing biological inference, and MetaPop provides a convenient tools package to explore the dual impact of macro- and micro-diversity across microbial communities.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 02, 2020.
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MetaPop: A pipeline for macro- and micro-diversity analyses and visualization of microbial and viral metagenome-derived populations
Ann C. Gregory, Kenji Gerhardt, Zhi-Ping Zhong, Benjamin Bolduc, Ben Temperton, Konstantinos T. Konstantinidis, Matthew B. Sullivan
bioRxiv 2020.11.01.363960; doi: https://doi.org/10.1101/2020.11.01.363960
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MetaPop: A pipeline for macro- and micro-diversity analyses and visualization of microbial and viral metagenome-derived populations
Ann C. Gregory, Kenji Gerhardt, Zhi-Ping Zhong, Benjamin Bolduc, Ben Temperton, Konstantinos T. Konstantinidis, Matthew B. Sullivan
bioRxiv 2020.11.01.363960; doi: https://doi.org/10.1101/2020.11.01.363960

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