Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes

Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the commu...

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Main Authors:	Nayfach, Stephen, Bradley, Patrick H., Wyman, Stacia K., Laurent, Timothy J., Williams, Alex, Eisen, Jonathan A., Pollard, Katherine S., Sharpton, Thomas J.
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643905/

id	pubmed-4643905
recordtype	oai_dc
spelling	pubmed-46439052015-11-18 Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes Nayfach, Stephen Bradley, Patrick H. Wyman, Stacia K. Laurent, Timothy J. Williams, Alex Eisen, Jonathan A. Pollard, Katherine S. Sharpton, Thomas J. Research Article Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn’s disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease. Public Library of Science 2015-11-13 /pmc/articles/PMC4643905/ /pubmed/26565399 http://dx.doi.org/10.1371/journal.pcbi.1004573 Text en © 2015 Nayfach et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Nayfach, Stephen Bradley, Patrick H. Wyman, Stacia K. Laurent, Timothy J. Williams, Alex Eisen, Jonathan A. Pollard, Katherine S. Sharpton, Thomas J.
spellingShingle	Nayfach, Stephen Bradley, Patrick H. Wyman, Stacia K. Laurent, Timothy J. Williams, Alex Eisen, Jonathan A. Pollard, Katherine S. Sharpton, Thomas J. Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes
author_facet	Nayfach, Stephen Bradley, Patrick H. Wyman, Stacia K. Laurent, Timothy J. Williams, Alex Eisen, Jonathan A. Pollard, Katherine S. Sharpton, Thomas J.
author_sort	Nayfach, Stephen
title	Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes
title_short	Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes
title_full	Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes
title_fullStr	Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes
title_full_unstemmed	Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes
title_sort	automated and accurate estimation of gene family abundance from shotgun metagenomes
description	Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn’s disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643905/
_version_	1613500860325691392

Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes

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