Identification of microbial biomarkers for colorectal cancer using strain-level metagenomic profiling

• Grant number: 16/23527-2
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): April 03, 2017
• Effective date (End): April 02, 2018
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: João Carlos Setubal
• Grantee: Andrew Maltez Thomas
• Supervisor abroad: Nicola Segata
• Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Local de pesquisa : Universitá degli Studi di Trento, Italy
• Associated to the scholarship: 15/01507-7 - Microbial community profiling of human cancers, BP.DR

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world, affecting more than 1.3 million people every year. CRCs can be divided into sporadic, inflammatory and hereditary forms. Genetics can, however, explain only a small proportion of disease variance. Using 16S rRNA amplicon sequencing, several bacterial species have been implicated in the development of CRC, but high-resolution microbial biomarkers are still missing. Very few studies have investigated CRC-associated changes of fecal microbiota and their potential as microbial biomarkers using high-resolution shotgun metagenomic data. Moreover, existing metagenomic studies adopted computational tools still unable to uncover the diversity within species, which is very limiting considering the inter-species variability of many microbial organisms. We will use metagenomic shotgun sequencing of fecal samples to identify strain-level taxonomic and functional biomarkers that distinguish CRC patients from tumor-free controls in an Italian cohort of 102 participants, divided in 75 CRC patients and 27 controls. Potential biomarkers will be validated in all publicly available fecal metagenomic CRC datasets. Concomitantly, we will identify and quantify trimethylamine (TMA) producing microbial enzymes in these datasets, in order to evaluate possible increases in choline metabolism in CRC patients. Altogether, we aim at identifying microbial biomarkers of CRC by exploiting novel strain-level computational methods on a newly sequenced CRC microbiome dataset and validate these biomarkers against publicly available data. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

THOMAS, ANDREW MALTEZ; MANGHI, PAOLO; ASNICAR, FRANCESCO; PASOLLI, EDOARDO; ARMANINI, FEDERICA; ZOLFO, MORENO; BEGHINI, FRANCESCO; MANARA, SERENA; KARCHER, NICOLAI; POZZI, CHIARA; GANDINI, SARA; SERRANO, DAVIDE; TARALLO, SONIA; FRANCAVILLA, ANTONIO; GALLO, GAETANO; TROMPETTO, MARIO; FERRERO, GIULIO; MIZUTANI, SAYAKA; SHIROMA, HIROTSUGU; SHIBA, SATOSHI; SHIBATA, TATSUHIRO; YACHIDA, SHINICHI; YAMADA, TAKUJI; WIRBEL, JAKOB; SCHROTZ-KING, PETRA; ULRICH, CORNELIA M.; BRENNER, HERMANN; ARUMUGAM, MANIMOZHIYAN; BORK, PEER; ZELLER, GEORG; CORDERO, FRANCESCA; DIAS-NETO, EMMANUEL; SETUBAL, JOAO CARLOS; TETT, ADRIAN; PARDINI, BARBARA; RESCIGNO, MARIA; WALDRON, LEVI; NACCARATI, ALESSIO; SEGATA, NICOLA. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nature Medicine, v. 25, n. 4, p. 667+, APR 2019. Web of Science Citations: 24.

WIRBEL, JAKOB; PYL, PAUL THEODOR; KARTAL, ECE; ZYCH, KONRAD; KASHANI, ALIREZA; MILANESE, ALESSIO; FLECK, JONAS S.; VOIGT, ANITA Y.; PALLEJA, ALBERT; PONNUDURAI, RUBY; SUNAGAWA, SHINICHI; COELHO, LUIS PEDRO; SCHROTZ-KING, PETRA; VOGTMANN, EMILY; HABERMANN, NINA; NIMEUS, EMMA; THOMAS, ANDREW M.; MANGHI, PAOLO; GANDINI, SARA; SERRANO, DAVIDE; MIZUTANI, SAYAKA; SHIROMA, HIROTSUGU; SHIBA, SATOSHI; SHIBATA, TATSUHIRO; YACHIDA, SHINICHI; YAMADA, TAKUJI; WALDRON, LEVI; NACCARATI, ALESSIO; SEGATA, NICOLA; SINHA, RASHMI; ULRICH, CORNELIA M.; BRENNER, HERMANN; ARUMUGAM, MANIMOZHIYAN; BORK, PEER; ZELLER, GEORG. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nature Medicine, v. 25, n. 4, p. 679+, APR 2019. Web of Science Citations: 30.