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

Systematic Characterization and Analysis of the Taxonomic Drivers of Functional Shifts in the Human Microbiome.
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DOI:
10.1016/j.chom.2016.12.014
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发表时间:
2017-02-08
影响因子:
30.3
通讯作者:
Borenstein E
Borenstein E
中科院分区:
医学1区
文献类型:
--
作者:
Manor O;Borenstein E

文献摘要

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人类微生物组的比较分析已经确定了与许多疾病相关的分类和功能变化。然而,迄今为止,微生物组的分类和功能研究大多是独立的,功能失衡的分类驱动因素尚未系统地确定。在这里,我们提出FishTaco,一个分析和计算框架,集成了分类和功能比较分析,以准确量化分类群水平对疾病相关功能转移的贡献。将FishTaco应用于几个大规模宏基因组队列,我们表明微生物组功能能力的变化可以追溯到特定的分类群。此外,驱动功能转移的类群及其贡献水平在不同功能间存在显著差异。我们还发现,不同疾病中类似的功能失衡是由疾病特异性和共享分类群驱动的。这种对微生物生态和功能动态的综合分析可以为未来基于微生物组的治疗提供信息,确定操纵微生物组功能能力的假定干预目标。比较人类微生物组分析已经确定了与疾病相关的分类和功能变化。Manor和Borenstein提出了一个综合的多组学框架,确定了功能转变的微生物驱动因素。它的应用表明,微生物组功能能力的变化可以追溯到功能、位点和疾病特异性分类群。
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 human microbiome analyses have identified both taxonomic and functional shifts associated with diseases. Manor and Borenstein present an integrative multi-omic framework that identifies the microbial drivers of functional shifts. Its application reveals that shifts in the microbiome’s functional capacity can be traced back to function-, site-, and disease-specific taxa.