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Original Paper

Editor's Choice - Free Access

Framework for the Integration of Genomics, Epigenomics and Transcriptomics in Complex Diseases

Pineda S.a, f · Gomez-Rubio P.a · Picornell A.a · Bessonov K.f · Márquez M.a · Kogevinas M.c, d · Real F.X.b, e · Van Steen K.f, g · Malats N.a

Author affiliations

aGenetic and Molecular Epidemiology Group, and bEpithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, cCentre for Research in Environmental Epidemiology (CREAL), dInstitut Municipal d'Investigació Mèdica - Hospital del Mar, and eDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; fSystems and Modeling Unit, Montefiore Institute, University of Liège, and gBioinformatics and Modeling, GIGA-R, University of Liège, Liège, Belgium

Corresponding Author

Nuria Malats, MD, MPH, PhD

Genetic and Molecular Epidemiology Group

Spanish National Cancer Research Centre (CNIO)

C/Melchor Fernández Almagro, 3, ES-28029 Madrid (Spain)

E-Mail nmalats@cnio.es

Prof. Kristel Van Steen, PhD, PhD

Systems and Modeling Unit, Montefiore Institute

University of Liège, Bât. B28 Bioinformatique, Grande Traverse 10

BE-4000 Liège (Belgium)

E-Mail kristel.vansteen@ulg.ac.be

Related Articles for ""

Hum Hered 2015;79:124-136

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Objectives: Different types of ‘-omics' data are becoming available in the post-genome era; still a single -omics assessment provides limited insights to understand the biological mechanism of complex diseases. Genomics, epigenomics and transcriptomics data provide insight into the molecular dysregulation of neoplastic diseases, among them urothelial bladder cancer (UBC). Here, we propose a detailed analytical framework necessary to achieve an adequate integration of the three sets of -omics data to ultimately identify previously hidden genetic mechanisms in UBC. Methods: We built a multi-staged framework to study possible pair-wise combinations and integrated the data in three-way relationships. SNP genotypes, CpG methylation levels and gene expression levels were determined for a total of 70 individuals with UBC and with fresh tumour tissue available. Results: We suggest two main hypothesis-based scenarios for gene regulation based on the -omics integration analysis, where DNA methylation affects gene expression and genetic variants co-regulate gene expression and DNA methylation. We identified several three-way trans-association ‘hotspots' that are found at the molecular level and that deserve further studies. Conclusions: The proposed integrative framework allowed us to identify relationships at the whole-genome level providing some new biological insights and highlighting the importance of integrating -omics data.

© 2015 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: July 28, 2015
Issue release date: July 2015

Number of Print Pages: 13
Number of Figures: 4
Number of Tables: 7

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

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