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

被引:730
作者
Abubucker, Sahar [1 ]
Segata, Nicola [2 ]
Goll, Johannes [3 ]
Schubert, Alyxandria M. [4 ]
Izard, Jacques [5 ,6 ]
Cantarel, Brandi L. [7 ]
Rodriguez-Mueller, Beltran [6 ]
Zucker, Jeremy [8 ]
Thiagarajan, Mathangi [3 ]
Henrissat, Bernard [9 ]
White, Owen [7 ]
Kelley, Scott T. [10 ]
Methe, Barbara [3 ]
Schloss, Patrick D. [4 ]
Gevers, Dirk [8 ]
Mitreva, Makedonka [1 ]
Huttenhower, Curtis [2 ,8 ]
机构
[1] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63130 USA
[2] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
[3] J Craig Venter Inst, Rockville, MD USA
[4] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA
[5] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA
[6] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA
[7] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA
[8] Broad Inst MIT & Harvard, Cambridge, MA USA
[9] Univ Mediterranee, UMR CNRS 6098, Marseille, France
[10] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA
基金
美国国家科学基金会;
关键词
ASSESSING FUNCTIONAL DIVERSITY; BETA-GLUCURONIDASE; GUT MICROBIOTA; GENE; BACTERIA; EXPRESSION; HEPARANASE; RESOURCE; PATHWAYS; SETS;
D O I
10.1371/journal.pcbi.1002358
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 http://huttenhower.sph.harvard.edu/humann. 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.
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页数:17
相关论文
共 72 条
  • [41] Optimizing Read Mapping to Reference Genomes to Determine Composition and Species Prevalence in Microbial Communities
    Martin, John
    Sykes, Sean
    Young, Sarah
    Kota, Karthik
    Sanka, Ravi
    Sheth, Nihar
    Orvis, Joshua
    Sodergren, Erica
    Wang, Zhengyuan
    Weinstock, George M.
    Mitreva, Makedonka
    [J]. PLOS ONE, 2012, 7 (06):
  • [42] Use of simulated data sets to evaluate the fidelity of metagenomic processing methods
    Mavromatis, Konstantinos
    Ivanova, Natalia
    Barry, Kerrie
    Shapiro, Harris
    Goltsman, Eugene
    McHardy, Alice C.
    Rigoutsos, Isidore
    Salamov, Asaf
    Korzeniewski, Frank
    Land, Miriam
    Lapidus, Alla
    Grigoriev, Igor
    Richardson, Paul
    Hugenholtz, Philip
    Kyrpides, Nikos C.
    [J]. NATURE METHODS, 2007, 4 (06) : 495 - 500
  • [43] A framework for human microbiome research
    Methe, Barbara A.
    Nelson, Karen E.
    Pop, Mihai
    Creasy, Heather H.
    Giglio, Michelle G.
    Huttenhower, Curtis
    Gevers, Dirk
    Petrosino, Joseph F.
    Abubucker, Sahar
    Badger, Jonathan H.
    Chinwalla, Asif T.
    Earl, Ashlee M.
    FitzGerald, Michael G.
    Fulton, Robert S.
    Hallsworth-Pepin, Kymberlie
    Lobos, Elizabeth A.
    Madupu, Ramana
    Magrini, Vincent
    Martin, John C.
    Mitreva, Makedonka
    Muzny, Donna M.
    Sodergren, Erica J.
    Versalovic, James
    Wollam, Aye M.
    Worley, Kim C.
    Wortman, Jennifer R.
    Young, Sarah K.
    Zeng, Qiandong
    Aagaard, Kjersti M.
    Abolude, Olukemi O.
    Allen-Vercoe, Emma
    Alm, Eric J.
    Alvarado, Lucia
    Andersen, Gary L.
    Anderson, Scott
    Appelbaum, Elizabeth
    Arachchi, Harindra M.
    Armitage, Gary
    Arze, Cesar A.
    Ayvaz, Tulin
    Baker, Carl C.
    Begg, Lisa
    Belachew, Tsegahiwot
    Bhonagiri, Veena
    Bihan, Monika
    Blaser, Martin J.
    Bloom, Toby
    Bonazzi, Vivien R.
    Brooks, Paul
    Buck, GregoryA.
    [J]. NATURE, 2012, 486 (7402) : 215 - 221
  • [44] The metagenomics RAST server - a public resource for the automatic phylogenetic and functional analysis of metagenomes
    Meyer, F.
    Paarmann, D.
    D'Souza, M.
    Olson, R.
    Glass, E. M.
    Kubal, M.
    Paczian, T.
    Rodriguez, A.
    Stevens, R.
    Wilke, A.
    Wilkening, J.
    Edwards, R. A.
    [J]. BMC BIOINFORMATICS, 2008, 9 (1)
  • [45] Functional analysis of metagenomes and metatranscriptomes using SEED and KEGG
    Mitra, Suparna
    Rupek, Paul
    Richter, Daniel C.
    Urich, Tim
    Gilbert, Jack A.
    Meyer, Folker
    Wilke, Andreas
    Huson, Daniel H.
    [J]. BMC BIOINFORMATICS, 2011, 12
  • [46] Functional diversity: back to basics and looking forward
    Petchey, Owen L.
    Gaston, Kevin J.
    [J]. ECOLOGY LETTERS, 2006, 9 (06) : 741 - 758
  • [47] Pielou E. C., 1975, Ecological Diversity
  • [48] A human gut microbial gene catalogue established by metagenomic sequencing
    Qin, Junjie
    Li, Ruiqiang
    Raes, Jeroen
    Arumugam, Manimozhiyan
    Burgdorf, Kristoffer Solvsten
    Manichanh, Chaysavanh
    Nielsen, Trine
    Pons, Nicolas
    Levenez, Florence
    Yamada, Takuji
    Mende, Daniel R.
    Li, Junhua
    Xu, Junming
    Li, Shaochuan
    Li, Dongfang
    Cao, Jianjun
    Wang, Bo
    Liang, Huiqing
    Zheng, Huisong
    Xie, Yinlong
    Tap, Julien
    Lepage, Patricia
    Bertalan, Marcelo
    Batto, Jean-Michel
    Hansen, Torben
    Le Paslier, Denis
    Linneberg, Allan
    Nielsen, H. Bjorn
    Pelletier, Eric
    Renault, Pierre
    Sicheritz-Ponten, Thomas
    Turner, Keith
    Zhu, Hongmei
    Yu, Chang
    Li, Shengting
    Jian, Min
    Zhou, Yan
    Li, Yingrui
    Zhang, Xiuqing
    Li, Songgang
    Qin, Nan
    Yang, Huanming
    Wang, Jian
    Brunak, Soren
    Dore, Joel
    Guarner, Francisco
    Kristiansen, Karsten
    Pedersen, Oluf
    Parkhill, Julian
    Weissenbach, Jean
    [J]. NATURE, 2010, 464 (7285) : 59 - U70
  • [49] Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data
    Raes, Jeroen
    Letunic, Ivica
    Yamada, Takuji
    Jensen, Lars Juhl
    Bork, Peer
    [J]. MOLECULAR SYSTEMS BIOLOGY, 2011, 7
  • [50] Vaginal microbiome of reproductive-age women
    Ravel, Jacques
    Gajer, Pawel
    Abdo, Zaid
    Schneider, G. Maria
    Koenig, Sara S. K.
    McCulle, Stacey L.
    Karlebach, Shara
    Gorle, Reshma
    Russell, Jennifer
    Tacket, Carol O.
    Brotman, Rebecca M.
    Davis, Catherine C.
    Ault, Kevin
    Peralta, Ligia
    Forney, Larry J.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 : 4680 - 4687