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Bioinformatic tool to integrate and understand aberrant epigenomic and genomic changes associated with cancer: methods, development and analysis

Grant number: 16/01389-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2016
Effective date (End): February 28, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Houtan Noushmehr
Grantee:Tiago Chedraoui Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:15/07925-5 - Open source software statistical tools to aid in analyzing and integrating large cancer epigenomic datasets in order to decipher and understand regulatory networks, AP.JP
Associated scholarship(s):16/10436-9 - Development and enhancement of bioinformatic tools to integrate and understand aberrant epigenomic and genomic changes associated with cancer: methods, development and analysis, BE.EP.DD

Abstract

Cancer, which is one of the major causes of mortality worldwide, is a complex disease orchestrated by aberrant genomic and epigenomic changes that can modify gene regulatory circuits and cellular identity. Emerging evidence obtained through high-throughput genomic data deposited within the public TCGA international consortium suggests that one in ten cancer patients would be more accurately classified by molecular taxonomy versus histology. Therefore, we have hypothesized that the establishment of genome-wide maps of the de novo DNA binding motifs localization coupled with differentially methylated regions and gene expression changes might help to characterize and exploit cancer phenotypes at the molecular level. Technological advances and public databases like The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (roadmap) have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high resolution. Markedly however, biological information is stored in different formats and there is no current tool to integrate the data, highlighting an urgent need to develop bioinformatic tools and/or computational softwares to overcome this challenge. In this context, the main purpose of this study is to implement the development of biOMICs, a package coded in the GNU GPL (General Public License) R programming language that will be submitted to the larger open-source Bioconductor community project. Our expectation is that biOMICs can effectively automate search, retrieve, and analyze the vast (epi)genomic data currently available from TCGA, ENCODE, and Roadmap, and integrate genomics and epigenomics features with researchers own high-throughput data. Furthermore, we will also navigate through these data manually in order to validate the capacity of biOMICs in discovering epigenomic signatures able to redefine subtypes of cancer. Finally, we will use biOMICs to investigate the molecular differences betwen two subgroups of gliomas, one of the most aggressive primary brain cancer, recently discovered by our laboratory. (AU)

Scientific publications (5)
(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)
SILVA, TIAGO C.; COETZEE, SIMON G.; GULL, NICOLE; YAO, LIJING; HAZELETT, DENNIS J.; NOUSHMEHR, HOUTAN; LIN, DE-CHEN; BERMAN, BENJAMIN R. ELMER v.2: an R/Bioconductor package to reconstruct gene regulatory networks from DNA methylation and transcriptome profiles. Bioinformatics, v. 35, n. 11, p. 1974-1977, JUN 1 2019. Web of Science Citations: 5.
MOUNIR, MOHAMED; LUCCHETTA, MARTA; SILVA, TIAGO C.; OLSEN, CATHARINA; BONTEMPI, GIANLUCA; CHEN, XI; NOUSHMEHR, HOUTAN; COLAPRICO, ANTONIO; PAPALEO, ELENA. New functionalities in the TCGAbiolinks package for the study and integration of cancer data from GDC and GTEx. PLOS COMPUTATIONAL BIOLOGY, v. 15, n. 3 MAR 2019. Web of Science Citations: 7.
MALTA, TATHIANE M.; DE SOUZA, CAMILA F.; SABEDOT, THAIS S.; SILVA, TIAGO C.; MOSELLA, MARITZA S.; KALKANIS, STEVEN N.; SNYDER, JAMES; CASTRO, ANA VALERIA B.; NOUSHMEHR, HOUTAN. Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications. NEURO-ONCOLOGY, v. 20, n. 5, p. 608-620, MAY 2018. Web of Science Citations: 19.
MALTA, TATHIANE M.; SOKOLOV, ARTEM; GENTLES, ANDREW J.; BURZYKOWSKI, TOMASZ; POISSON, LAILA; WEINSTEIN, JOHN N.; KAMINSKA, BOZENA; HUELSKEN, JOERG; OMBERG, LARSSON; GEVAERT, OLIVIER; COLAPRICO, ANTONIO; CZERWINSKA, PATRYCJA; MAZUREK, SYLWIA; MISHRA, LOPA; HEYN, HOLGER; KRASNITZ, ALEX; GODWIN, ANDREW K.; LAZAR, ALEXANDER J.; STUART, JOSHUA M.; HOADLEY, KATHERINE A.; LAIRD, PETER W.; NOUSHMEHR, HOUTAN; WIZNEROWICZ, MACIEJ; NETWORK, CANCER GENOME ATLAS RES. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. Cell, v. 173, n. 2, p. 338+, APR 5 2018. Web of Science Citations: 92.
CAVA, CLAUDIA; COLAPRICO, ANTONIO; BERTOLI, GLORIA; GRAUDENZI, ALEX; SILVA, TIAGO C.; OLSEN, CATHARINA; NOUSHMEHR, HOUTAN; BONTEMPI, GIANLUCA; MAURI, GIANCARLO; CASTIGLIONI, ISABELLA. SpidermiR: An R/Bioconductor Package for Integrative Analysis with miRNA Data. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 2 FEB 2017. Web of Science Citations: 19.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Tiago Chedraoui. Bioinformatic tool to integrate and understand aberrant epigenomic and genomic changes associated with cancer: Methods, development and analysis. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.