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Grant Details

Grant Number: 5R01CA230551-03 Interpret this number
Primary Investigator: Waldron, Levi
Organization: Graduate School Of Public Health And Health Policy
Project Title: Exploiting Public Metagenomic Data to Uncover Cancer-Microbiome Relationships
Fiscal Year: 2021


Abstract

Project Summary / Abstract The microbiome is now known to influence the onset, progression, and treatment of cancers both within the gastrointestinal tract and systemically. Whole-metagenome shotgun sequencing (WMS) provides the highest resolution profiling of the human bacterial, archeal, and viral microbiome available, however, it remains expensive to perform. Furthermore, the analysis of all microbiome data, including WMS and the less expensive 16S ribosomal RNA amplicon sequencing, is hindered by inability to systematically compare the results to previous studies and experiments. Thus, high quality re-analysis of public microbiome data offers the opportunity for rapid and cost-effective elucidation of the roles of bacteria, viruses, and microbial function in the etiology and progression of cancer. This proposal efficiently extracts new value from published microbiome research through three aims. First, it improves the interpretability of cancer-linked microbiome profiles by translating concepts from Gene Set Enrichment Analysis and developing microbial signature resources. Second, it develops new methods to identify strain-level microbial features, fungi, human viruses, and bacteriophages from WMS data and applies these to thousands of available cancer-associated metagenomes and controls. Finally, it identifies microbiota, community structure and functions relevant in the development or inhibition of cancer by pooled analysis and meta-analysis of publicly available human microbiome profiles, and makes these newly processed data and manually curated clinical data conveniently available to the cancer research community for further interrogation. This contribution is significant because it increases the likelihood of identifying new microbiome correlates of cancer, of correctly distinguishing causal factors from artifacts of confounding or technical batches, and of developing effective public health interventions based on the human microbiome. The proposed research is innovative because it identifies and corrects important deficiencies in how microbiome data are processed, interpreted, and made available for re-use on a large scale by other research teams.



Publications

Prevotella diversity, niches and interactions with the human host.
Authors: Tett A. , Pasolli E. , Masetti G. , Ercolini D. , Segata N. .
Source: Nature reviews. Microbiology, 2021 09; 19(9), p. 585-599.
EPub date: 2021-05-28.
PMID: 34050328
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Blue poo: impact of gut transit time on the gut microbiome using a novel marker.
Authors: Asnicar F. , Leeming E.R. , Dimidi E. , Mazidi M. , Franks P.W. , Al Khatib H. , Valdes A.M. , Davies R. , Bakker E. , Francis L. , et al. .
Source: Gut, 2021 Sep; 70(9), p. 1665-1674.
EPub date: 2021-03-15.
PMID: 33722860
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Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly.
Authors: Karcher N. , Nigro E. , Punčochář M. , Blanco-Míguez A. , Ciciani M. , Manghi P. , Zolfo M. , Cumbo F. , Manara S. , Golzato D. , et al. .
Source: Genome biology, 2021-07-14; 22(1), p. 209.
EPub date: 2021-07-14.
PMID: 34261503
Related Citations

Genes Encoding Microbial Acyl Coenzyme A Binding Protein/Diazepam-Binding Inhibitor Orthologs Are Rare in the Human Gut Microbiome and Show No Links to Obesity.
Authors: Thomas A.M. , Asnicar F. , Kroemer G. , Segata N. .
Source: Applied and environmental microbiology, 2021-05-26; 87(12), p. e0047121.
EPub date: 2021-05-26.
PMID: 33837018
Related Citations

Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3.
Authors: Beghini F. , McIver L.J. , Blanco-Míguez A. , Dubois L. , Asnicar F. , Maharjan S. , Mailyan A. , Manghi P. , Scholz M. , Thomas A.M. , et al. .
Source: eLife, 2021-05-04; 10, .
EPub date: 2021-05-04.
PMID: 33944776
Related Citations

High intake of vegetables is linked to lower white blood cell profile and the effect is mediated by the gut microbiome.
Authors: Menni C. , Louca P. , Berry S.E. , Vijay A. , Astbury S. , Leeming E.R. , Gibson R. , Asnicar F. , Piccinno G. , Wolf J. , et al. .
Source: BMC medicine, 2021-02-11; 19(1), p. 37.
EPub date: 2021-02-11.
PMID: 33568158
Related Citations

Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals.
Authors: Asnicar F. , Berry S.E. , Valdes A.M. , Nguyen L.H. , Piccinno G. , Drew D.A. , Leeming E. , Gibson R. , Le Roy C. , Khatib H.A. , et al. .
Source: Nature medicine, 2021 02; 27(2), p. 321-332.
EPub date: 2021-01-11.
PMID: 33432175
Related Citations

Multiomic Analysis of Subtype Evolution and Heterogeneity in High-Grade Serous Ovarian Carcinoma.
Authors: Geistlinger L. , Oh S. , Ramos M. , Schiffer L. , LaRue R.S. , Henzler C.M. , Munro S.A. , Daughters C. , Nelson A.C. , Winterhoff B.J. , et al. .
Source: Cancer research, 2020-10-15; 80(20), p. 4335-4345.
EPub date: 2020-08-03.
PMID: 32747365
Related Citations

Assessment of statistical methods from single cell, bulk RNA-seq, and metagenomics applied to microbiome data.
Authors: Calgaro M. , Romualdi C. , Waldron L. , Risso D. , Vitulo N. .
Source: Genome biology, 2020-08-03; 21(1), p. 191.
EPub date: 2020-08-03.
PMID: 32746888
Related Citations

Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations.
Authors: Karcher N. , Pasolli E. , Asnicar F. , Huang K.D. , Tett A. , Manara S. , Armanini F. , Bain D. , Duncan S.H. , Louis P. , et al. .
Source: Genome biology, 2020-06-08; 21(1), p. 138.
EPub date: 2020-06-08.
PMID: 32513234
Related Citations

Human postprandial responses to food and potential for precision nutrition.
Authors: Berry S.E. , Valdes A.M. , Drew D.A. , Asnicar F. , Mazidi M. , Wolf J. , Capdevila J. , Hadjigeorgiou G. , Davies R. , Al Khatib H. , et al. .
Source: Nature medicine, 2020 06; 26(6), p. 964-973.
EPub date: 2020-06-11.
PMID: 32528151
Related Citations

Precise phylogenetic analysis of microbial isolates and genomes from metagenomes using PhyloPhlAn 3.0.
Authors: Asnicar F. , Thomas A.M. , Beghini F. , Mengoni C. , Manara S. , Manghi P. , Zhu Q. , Bolzan M. , Cumbo F. , May U. , et al. .
Source: Nature communications, 2020-05-19; 11(1), p. 2500.
EPub date: 2020-05-19.
PMID: 32427907
Related Citations

Waldron et al. Reply to "Commentary on the HMP16SData Bioconductor Package".
Authors: Waldron L. , Schiffer L. , Azhar R. , Ramos M. , Geistlinger L. , Segata N. .
Source: American journal of epidemiology, 2019-06-01; 188(6), p. 1031-1032.
PMID: 30689687
Related Citations

HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.
Authors: Schiffer L. , Azhar R. , Shepherd L. , Ramos M. , Geistlinger L. , Huttenhower C. , Dowd J.B. , Segata N. , Waldron L. .
Source: American journal of epidemiology, 2019-06-01; 188(6), p. 1023-1026.
PMID: 30649166
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