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000143427 1001_ $$00000-0001-5789-3354$$aThomas, Andrew Maltez$$b0
000143427 245__ $$aMetagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation.
000143427 260__ $$aNew York, NY$$bNature America Inc.$$c2019
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000143427 520__ $$aSeveral 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.
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000143427 7001_ $$aManghi, Paolo$$b1
000143427 7001_ $$00000-0003-3732-1468$$aAsnicar, Francesco$$b2
000143427 7001_ $$aPasolli, Edoardo$$b3
000143427 7001_ $$aArmanini, Federica$$b4
000143427 7001_ $$00000-0001-6661-4046$$aZolfo, Moreno$$b5
000143427 7001_ $$00000-0002-8105-9607$$aBeghini, Francesco$$b6
000143427 7001_ $$aManara, Serena$$b7
000143427 7001_ $$aKarcher, Nicolai$$b8
000143427 7001_ $$aPozzi, Chiara$$b9
000143427 7001_ $$00000-0002-1348-4548$$aGandini, Sara$$b10
000143427 7001_ $$aSerrano, Davide$$b11
000143427 7001_ $$00000-0003-0887-2607$$aTarallo, Sonia$$b12
000143427 7001_ $$00000-0003-1594-2837$$aFrancavilla, Antonio$$b13
000143427 7001_ $$00000-0003-1066-4671$$aGallo, Gaetano$$b14
000143427 7001_ $$aTrompetto, Mario$$b15
000143427 7001_ $$00000-0002-4580-0680$$aFerrero, Giulio$$b16
000143427 7001_ $$aMizutani, Sayaka$$b17
000143427 7001_ $$aShiroma, Hirotsugu$$b18
000143427 7001_ $$aShiba, Satoshi$$b19
000143427 7001_ $$00000-0002-0477-210X$$aShibata, Tatsuhiro$$b20
000143427 7001_ $$aYachida, Shinichi$$b21
000143427 7001_ $$aYamada, Takuji$$b22
000143427 7001_ $$00000-0002-4073-3562$$aWirbel, Jakob$$b23
000143427 7001_ $$0P:(DE-He78)01ef71f71b01a3ec3b698653fd43fe86$$aSchrotz-King, Petra$$b24$$udkfz
000143427 7001_ $$aUlrich, Cornelia M$$b25
000143427 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b26$$udkfz
000143427 7001_ $$00000-0002-0886-9101$$aArumugam, Manimozhiyan$$b27
000143427 7001_ $$00000-0002-2627-833X$$aBork, Peer$$b28
000143427 7001_ $$00000-0003-1429-7485$$aZeller, Georg$$b29
000143427 7001_ $$aCordero, Francesca$$b30
000143427 7001_ $$00000-0001-5670-8559$$aDias-Neto, Emmanuel$$b31
000143427 7001_ $$aSetubal, João Carlos$$b32
000143427 7001_ $$aTett, Adrian$$b33
000143427 7001_ $$00000-0001-9571-4257$$aPardini, Barbara$$b34
000143427 7001_ $$aRescigno, Maria$$b35
000143427 7001_ $$00000-0003-2725-0694$$aWaldron, Levi$$b36
000143427 7001_ $$00000-0001-5774-0905$$aNaccarati, Alessio$$b37
000143427 7001_ $$00000-0002-1583-5794$$aSegata, Nicola$$b38
000143427 773__ $$0PERI:(DE-600)1484517-9$$a10.1038/s41591-019-0405-7$$gVol. 25, no. 4, p. 667 - 678$$n4$$p667 - 678$$tNature medicine$$v25$$x1546-170X$$y2019
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