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@ARTICLE{Thomas:143427,
author = {A. M. Thomas and P. Manghi and F. Asnicar and E. Pasolli
and F. Armanini and M. Zolfo and F. Beghini and S. Manara
and N. Karcher and C. Pozzi and S. Gandini and D. Serrano
and S. Tarallo and A. Francavilla and G. Gallo and M.
Trompetto and G. Ferrero and S. Mizutani and H. Shiroma and
S. Shiba and T. Shibata and S. Yachida and T. Yamada and J.
Wirbel and P. Schrotz-King$^*$ and C. M. Ulrich and H.
Brenner$^*$ and M. Arumugam and P. Bork and G. Zeller and F.
Cordero and E. Dias-Neto and J. C. Setubal and A. Tett and
B. Pardini and M. Rescigno and L. Waldron and A. Naccarati
and N. Segata},
title = {{M}etagenomic analysis of colorectal cancer datasets
identifies cross-cohort microbial diagnostic signatures and
a link with choline degradation.},
journal = {Nature medicine},
volume = {25},
number = {4},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2019-01015},
pages = {667 - 678},
year = {2019},
abstract = {Several studies have investigated links between the gut
microbiome and colorectal cancer (CRC), but questions remain
about the replicability of biomarkers across cohorts and
populations. We performed a meta-analysis of five publicly
available datasets and two new cohorts and validated the
findings on two additional cohorts, considering in total
969 fecal metagenomes. Unlike microbiome shifts associated
with gastrointestinal syndromes, the gut microbiome in CRC
showed reproducibly higher richness than controls
(P < 0.01), partially due to expansions of species
typically derived from the oral cavity. Meta-analysis of the
microbiome functional potential identified gluconeogenesis
and the putrefaction and fermentation pathways as being
associated with CRC, whereas the stachyose and starch
degradation pathways were associated with controls.
Predictive microbiome signatures for CRC trained on multiple
datasets showed consistently high accuracy in datasets not
considered for model training and independent validation
cohorts (average area under the curve, 0.84). Pooled
analysis of raw metagenomes showed that the choline
trimethylamine-lyase gene was overabundant in CRC
(P = 0.001), identifying a relationship between
microbiome choline metabolism and CRC. The combined analysis
of heterogeneous CRC cohorts thus identified reproducible
microbiome biomarkers and accurate disease-predictive models
that can form the basis for clinical prognostic tests and
hypothesis-driven mechanistic studies.},
cin = {C120 / C070 / L101},
ddc = {610},
cid = {I:(DE-He78)C120-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)L101-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30936548},
doi = {10.1038/s41591-019-0405-7},
url = {https://inrepo02.dkfz.de/record/143427},
}