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Cell Host Microbe. 2017 Feb 8;21(2):254-267. doi: 10.1016/j.chom.2016.12.014. Epub 2017 Jan 19.

Systematic Characterization and Analysis of the Taxonomic Drivers of Functional Shifts in the Human Microbiome.

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Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA; Santa Fe Institute, Santa Fe, NM 87501, USA. Electronic address:


Comparative analyses of the human microbiome have identified both taxonomic and functional shifts that are associated with numerous diseases. To date, however, microbiome taxonomy and function have mostly been studied independently and the taxonomic drivers of functional imbalances have not been systematically identified. Here, we present FishTaco, an analytical and computational framework that integrates taxonomic and functional comparative analyses to accurately quantify taxon-level contributions to disease-associated functional shifts. Applying FishTaco to several large-scale metagenomic cohorts, we show that shifts in the microbiome's functional capacity can be traced back to specific taxa. Furthermore, the set of taxa driving functional shifts and their contribution levels vary markedly between functions. We additionally find that similar functional imbalances in different diseases are driven by both disease-specific and shared taxa. Such integrated analysis of microbiome ecological and functional dynamics can inform future microbiome-based therapy, pinpointing putative intervention targets for manipulating the microbiome's functional capacity.


comparative analysis; compositional shifts; functional metagenomics; human microbiome; integrative analysis; microbial drivers; multi-omics; taxonomic profiling

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