Grant Details
Grant Number: |
5U01CA230551-02 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: |
2020 |
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
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