Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome

Abubucker, Sahar and Segata, Nicola and Goll, Johannes and Schubert, Alyxandria M. and Izard, Jacques and Cantarel, Brandi L. and Rodriguez-Mueller, Beltran and Zucker, Jeremy and Thiagarajan, Mathangi and Henrissat, Bernard and White, Owen and Kelley, Scott T. and Methe, Barbara and Achloss, Patrick D. and Gevers, Dirk and Mitreva, Makedonka and Huttenhower, Curtis (2012) Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome. PLoS Computational Biology, 8 (6). pp. 1-17.

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Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such
communities’ metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and
metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by
different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future
metagenomic studies.

Item Type: Article
Subjects: Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Marija Kalejska
Date Deposited: 30 Nov 2012 15:19
Last Modified: 30 Nov 2012 15:19

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