Person:
Izard, Jacques Georges

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Izard

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Jacques Georges

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Izard, Jacques Georges

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    Publication
    Metagenomic biomarker discovery and explanation
    (Springer Science + Business Media, 2011) Segata, Nicola; Izard, Jacques Georges; Waldron, Levi; Gevers, Dirk; Miropolsky, Larisa; Garrett, Wendy; Huttenhower, Curtis
    This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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    A Framework for Human Microbiome Research
    (Nature Publishing Group, 2012) Methé, Barbara A.; Nelson, Karen E.; Pop, Mihai; Creasy, Heather H.; Giglio, Michelle G.; Gevers, Dirk; Petrosino, Joseph F.; Abubucker, Sahar; Badger, Jonathan H.; Chinwalla, Asif T.; Earl, Ashlee M.; Fulton, Robert S.; Hallsworth-Pepin, Kymberlie; Lobos, Elizabeth A.; Madupu, Ramana; Magrini, Vincent; Mitreva, Makedonka; Muzny, Donna M.; Sodergren, Erica J.; Versalovic, James; Wollam, Aye M.; Worley, Kim C.; Wortman, Jennifer R.; Zeng, Qiandong; Aagaard, Kjersti M.; Abolude, Olukemi O.; Allen-Vercoe, Emma; Alm, Eric J.; Alvarado, Lucia; Andersen, Gary L.; 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; Vivien Bonazzi, J.; Brooks, Paul; Buck, Gregory A.; Buhay, Christian J.; Busam, Dana A.; Campbell, Joseph L.; Canon, Shane R.; Cantarel, Brandi L.; Chain, Patrick S.; Chen, I-Min A.; Chen, Lei; Chhibba, Shaila; Ciulla, Dawn M.; Clemente, Jose C.; Clifton, Sandra W.; Conlan, Sean; Crabtree, Jonathan; Cutting, Mary A.; Davidovics, Noam J.; Davis, Catherine C.; DeSantis, Todd Z.; Deal, Carolyn; Delehaunty, Kimberley D.; Deych, Elena; Dooling, David J.; Dugan, Shannon P.; Farmer, Candace N.; Faust, Karoline; Feldgarden, Michael; Felix, Victor M.; Fisher, Sheila; Fodor, Anthony A.; Forney, Larry; Foster, Leslie; Di Francesco, Valentina; Friedman, Jonathan; Friedrich, Dennis C.; Fronick, Catrina C.; Fulton, Lucinda L.; Gao, Hongyu; Garcia, Nathalia; Giannoukos, Georgia; Giblin, Christina; Giovanni, Maria Y.; Goll, Johannes; Gonzalez, Antonio; Griggs, Allison; Gujja, Sharvari; Haas, Brian J.; Hamilton, Holli A.; Hepburn, Theresa A.; Herter, Brandi; Hoffmann, Diane E.; Holder, Michael E.; Howarth, Clinton; Huse, Susan M.; Jansson, Janet K.; Jiang, Huaiyang; Jordan, Catherine; Joshi, Vandita; Katancik, James A.; Keitel, Wendy A.; Kelley, Scott T.; Kells, Cristyn; Kinder-Haake, Susan; King, Nicholas B.; Knight, Rob; Kong, Heidi H.; Koren, Omry; Koren, Sergey; Kota, Karthik C.; Kovar, Christie L.; Kyrpides, Nikos C.; La Rosa, Patricio S.; Lewis, Cecil M.; Lewis, Lora; Ley, Ruth E.; Li, Kelvin; Liolios, Konstantinos; Lo, Chien-Chi; Lozupone, Catherine A.; Lunsford, R. Dwayne; Madden, Tessa; Mahurkar, Anup A.; Mannon, Peter J.; Mardis, Elaine R.; Markowitz, Victor M.; Mavrommatis, Konstantinos; McCorrison, Jamison M.; McEwen, Jean; McGuire, Amy L.; McInnes, Pamela; Mehta, Teena; Mihindukulasuriya, Kathie A.; Minx, Patrick J.; Newsham, Irene; Nusbaum, Chad; O’Laughlin, Michelle; Orvis, Joshua; Pagani, Ioanna; Palaniappan, Krishna; Patel, Shital M.; Peterson, Jane; Podar, Mircea; Pohl, Craig; Pollard, Katherine S.; Priest, Margaret E.; Proctor, Lita M.; Qin, Xiang; Raes, Jeroen; Ravel, Jacques; Reid, Jeffrey G.; Rho, Mina; Rhodes, Rosamond; Riehle, Kevin P.; Rivera, Maria C.; Rodriguez-Mueller, Beltran; Rogers, Yu-Hui; Ross, Matthew C.; Russ, Carsten; Sanka, Ravi K.; Pamela Sankar, J.; Sathirapongsasuti, Fah; Schloss, Jeffery A.; Schloss, Patrick D.; Scholz, Matthew; Schriml, Lynn; Schubert, Alyxandria M.; Segata, Nicola; Segre, Julia A.; Shannon, William D.; Sharp, Richard R.; Sharpton, Thomas J.; Shenoy, Narmada; Sheth, Nihar U.; Simone, Gina A.; Singh, Indresh; Sobel, Jack D.; Sommer, Daniel D.; Spicer, Paul; Sutton, Granger G.; Tabbaa, Diana G.; Thiagarajan, Mathangi; Tomlinson, Chad M.; Torralba, Manolito; Treangen, Todd J.; Truty, Rebecca M.; Vishnivetskaya, Tatiana A.; Walker, Jason; Wang, Zhengyuan; Ward, Doyle V.; Warren, Wesley; Watson, Mark A.; Wellington, Christopher; Wetterstrand, Kris A.; Wilczek-Boney, Katarzyna; Wu, Yuan Qing; Wylie, Kristine M.; Wylie, Todd; Yandava, Chandri; Ye, Yuzhen; Yooseph, Shibu; Youmans, Bonnie P.; Zhou, Yanjiao; Zhu, Yiming; Zoloth, Laurie; Birren, Bruce W.; Gibbs, Richard A.; Highlander, Sarah K.; Weinstock, George M.; White, Owen; Huttenhower, Curtis; FitzGerald, Michael G.; Martin, John C.; Young, Sarah K.; Anderson, Scott; Chu, Ken; Dewhirst, Floyd; Ding, Yan; Dunne, Wm. Michael; Durkin, A. Scott; Edgar, Robert C.; Erlich, R; Farrell, Ruth M.; Goldberg, Jonathan M.; Harris, Emily L.; Huang, Katherine H.; Izard, Jacques Georges; Knights, Dan; Lee, Sandra L.; Lemon, Katherine; Lennon, Niall; Liu, Bo; Liu, Yue; McDonald, Daniel; Miller, Jason R.; Pearson, Matthew; Schmidt, Thomas M.; Smillie, Chris; Sykes, Sean M.; Wang, Lu; White, James R.; Ye, Liang; Zhang, Lan; Zucker, Jeremy Daniel Hofeld; Wilson, Richard K.
    A variety of microbial communities and their genes (microbiome) exist throughout the human body, playing fundamental roles in human health and disease. The NIH funded Human Microbiome Project (HMP) Consortium has established a population-scale framework which catalyzed significant development of metagenomic protocols resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 to 18 body sites up to three times, which to date, have generated 5,177 microbial taxonomic profiles from 16S rRNA genes and over 3.5 Tb of metagenomic sequence. In parallel, approximately 800 human-associated reference genomes have been sequenced. Collectively, these data represent the largest resource to date describing the abundance and variety of the human microbiome, while providing a platform for current and future studies.
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    Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome
    (Public Library of Science, 2012) Abubucker, Sahar; Goll, Johannes; Schubert, Alyxandria M.; Cantarel, Brandi L.; Rodriguez-Mueller, Beltran; Thiagarajan, Mathangi; Henrissat, Bernard; White, Owen; Kelley, Scott T.; Methé, Barbara; Schloss, Patrick D.; Gevers, Dirk; Mitreva, Makedonka; Segata, Nicola; Izard, Jacques Georges; Zucker, Jeremy Daniel Hofeld; Huttenhower, Curtis
    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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    Composition of the Adult Digestive Tract Bacterial Microbiome Based on Seven Mouth Surfaces, Tonsils, Throat and Stool Samples
    (BioMed Central, 2012) Segata, Nicholas; Haake, Susan Kinder; Mannon, Peter; Lemon, Katherine; Waldron, Levi; Gevers, Dirk; Huttenhower, Curtis; Izard, Jacques Georges
    Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body's greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites. Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. Phyla initially identified from environmental samples were detected throughout this population, primarily TM7, SR1, and Synergistetes. Genera with pathogenic members were well-represented among this disease-free cohort. Tooth-associated communities were distinct, but not entirely dissimilar, from other oral surfaces. The Porphyromonadaceae, Veillonellaceae and Lachnospiraceae families were common to all sites, but the distributions of their genera varied significantly. Most metabolic processes were distributed widely throughout the digestive tract microbiota, with variations in metagenomic abundance between body habitats. These included shifts in sugar transporter types between the supragingival plaque, other oral surfaces, and stool; hydrogen and hydrogen sulfide production were also differentially distributed. Conclusions: The microbiomes of ten digestive tract sites separated into four types based on composition. A core set of metabolic pathways was present across these diverse digestive tract habitats. These data provide a critical baseline for future studies investigating local and systemic diseases affecting human health.
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    Microbial Community Function and Biomarker Discovery in the Human Microbiome
    (BioMed Central, 2011) Abubucker, Sahar; Goll, Johannes; Schubert, Alyxandria M; Cantarel, Brandi L; Rodriguez-Mueller, Beltran; Thiagarajan, Mathangi; Henrissat, Bernard; White, Owen; Kelley, Scott T; Methé, Barbara; Schloss, Patrick D; Gevers, Dirk; Mitreva, Makedonka; Izard, Jacques Georges; Waldron, Levi; Zucker, Jeremy Daniel Hofeld; Garrett, Wendy; Huttenhower, Curtis; Segata, Nicola
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    Microbial Co-occurrence Relationships in the Human Microbiome
    (Public Library of Science, 2012) Faust, Karoline; Sathirapongsasuti, Jarupon Fah; Izard, Jacques Georges; Segata, Nicola; Gevers, Dirk; Raes, Jeroen; Huttenhower, Curtis
    The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles of this cohort, resulting in a global network of 3,005 significant co-occurrence and co-exclusion relationships between 197 clades occurring throughout the human microbiome. This network revealed strong niche specialization, with most microbial associations occurring within body sites and a number of accompanying inter-body site relationships. Microbial communities within the oropharynx grouped into three distinct habitats, which themselves showed no direct influence on the composition of the gut microbiota. Conversely, niches such as the vagina demonstrated little to no decomposition into region-specific interactions. Diverse mechanisms underlay individual interactions, with some such as the co-exclusion of Porphyromonaceae family members and Streptococcus in the subgingival plaque supported by known biochemical dependencies. These differences varied among broad phylogenetic groups as well, with the Bacilli and Fusobacteria, for example, both enriched for exclusion of taxa from other clades. Comparing phylogenetic versus functional similarities among bacteria, we show that dominant commensal taxa (such as Prevotellaceae and Bacteroides in the gut) often compete, while potential pathogens (e.g. Treponema and Prevotella in the dental plaque) are more likely to co-occur in complementary niches. This approach thus serves to open new opportunities for future targeted mechanistic studies of the microbial ecology of the human microbiome.