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Nat Methods. 2018 Nov;15(11):962-968. doi: 10.1038/s41592-018-0176-y. Epub 2018 Oct 30.

Species-level functional profiling of metagenomes and metatranscriptomes.

Author information

1
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
2
The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
3
Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
4
Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
5
Department of Computer Science & Engineering, University of California San Diego, San Diego, CA, USA.
6
Centre for Integrative Biology, University of Trento, Trento, Italy.
7
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. chuttenh@hsph.harvard.edu.
8
The Broad Institute of MIT and Harvard, Cambridge, MA, USA. chuttenh@hsph.harvard.edu.

Abstract

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types.

PMID:
30377376
PMCID:
PMC6235447
[Available on 2019-04-30]
DOI:
10.1038/s41592-018-0176-y

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