Species-level functional profiling of metagenomes and metatranscriptomes

Eric A. Franzosa, Lauren J. McIver, Gholamali Rahnavard, Luke R. Thompson, Melanie Schirmer, George Weingart, Karen Schwarzberg Lipson, Rob Knight, J. Gregory Caporaso, Nicola Segata, Curtis Huttenhower

Research output: Contribution to journalArticlepeer-review

899 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)962-968
Number of pages7
JournalNature Methods
Issue number11
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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