Graph-based variant discovery reveals novel dynamics in the human microbiome

Fuente: arXiv
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Auteurs principaux: Muralidharan, Harihara Subrahmaniam, Michaelis, Jacquelyn S, Ghurye, Jay, Treangen, Todd, Koren, Sergey, Fedarko, Marcus, Pop, Mihai
Format: Preprint
Publié: 2024
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author Muralidharan, Harihara Subrahmaniam
Michaelis, Jacquelyn S
Ghurye, Jay
Treangen, Todd
Koren, Sergey
Fedarko, Marcus
Pop, Mihai
author_facet Muralidharan, Harihara Subrahmaniam
Michaelis, Jacquelyn S
Ghurye, Jay
Treangen, Todd
Koren, Sergey
Fedarko, Marcus
Pop, Mihai
contents Sequence differences between the strains of bacteria comprising host-associated and environmental microbiota may play a role in community assembly and influence the resilience of microbial communities to disturbances. Tools for characterizing strain-level variation within microbial communities, however, are limited in scope, focusing on just single nucleotide polymorphisms, or relying on reference-based analyses that miss complex functional and structural variants. Here, we demonstrate the power of assembly graph analysis to detect and characterize structural variants in almost 1,000 metagenomes generated as part of the Human Microbiome Project. We identify over nine million variants comprising insertion/deletion events, repeat copy-number changes, and mobile elements such as plasmids. We highlight some of the potential functional roles of these genomic changes. Our analysis revealed striking differences in the rate of variation across body sites, highlighting niche-specific mechanisms of bacterial adaptation. The structural variants we detect also include potentially novel prophage integration events, highlighting the potential use of graph-based analyses for phage discovery.
format Preprint
id arxiv_https___arxiv_org_abs_2403_01610
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Graph-based variant discovery reveals novel dynamics in the human microbiome
Muralidharan, Harihara Subrahmaniam
Michaelis, Jacquelyn S
Ghurye, Jay
Treangen, Todd
Koren, Sergey
Fedarko, Marcus
Pop, Mihai
Genomics
Sequence differences between the strains of bacteria comprising host-associated and environmental microbiota may play a role in community assembly and influence the resilience of microbial communities to disturbances. Tools for characterizing strain-level variation within microbial communities, however, are limited in scope, focusing on just single nucleotide polymorphisms, or relying on reference-based analyses that miss complex functional and structural variants. Here, we demonstrate the power of assembly graph analysis to detect and characterize structural variants in almost 1,000 metagenomes generated as part of the Human Microbiome Project. We identify over nine million variants comprising insertion/deletion events, repeat copy-number changes, and mobile elements such as plasmids. We highlight some of the potential functional roles of these genomic changes. Our analysis revealed striking differences in the rate of variation across body sites, highlighting niche-specific mechanisms of bacterial adaptation. The structural variants we detect also include potentially novel prophage integration events, highlighting the potential use of graph-based analyses for phage discovery.
title Graph-based variant discovery reveals novel dynamics in the human microbiome
topic Genomics
url https://arxiv.org/abs/2403.01610