TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages

Tiago C Silva; Antonio Colaprico; Catharina Olsen; Fulvio D'Angelo; Gianluca Bontempi; Michele Ceccarelli; Houtan Noushmehr

doi:10.12688/f1000research.8923.2

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages

F1000Res. 2016 Jun 29:5:1542. doi: 10.12688/f1000research.8923.2. eCollection 2016.

Authors

Tiago C Silva¹, Antonio Colaprico², Catharina Olsen², Fulvio D'Angelo³, Gianluca Bontempi⁴, Michele Ceccarelli⁵, Houtan Noushmehr⁶

Affiliations

¹ Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Department of Biomedical Sciences, Cedars-Sinai, Los Angeles, CA, USA.
² Interuniversity Institute of Bioinformatics in Brussels, Brussels, Belgium; Machine Learning Group, ULB, Brussels, Belgium.
³ Department of Science and Technology, University of Sannio, Benevento, Italy; Biogem, Istituto di Ricerche Genetiche Gaetano Salvatore, Avellino, Italy.
⁴ Interuniversity Institute of Bioinformatics in Brussels, Brussels, Belgium; Machine Learning Group, ULB, Brussels, Belgium; Department of Science and Technology, University of Sannio, Benevento, Italy.
⁵ Qatar Computing Research Institute (QCRI), HBKU, Doha, Qatar.
⁶ Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA.

Abstract

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox, TCGAbiolinks.

Keywords: Bioinformatics; Cancer; ENCODE; Epigenomics; Genomics; Roadmap; TCGA; non-coding.

Grants and funding

The project was supported by the São Paulo Research Foundation ( FAPESP) (2015/02844-7 and 2016/01389-7 to T.C.S. & H.N. and 2015/07925-5 to H.N.), the BridgeIRIS project, funded by INNOVIRIS, Region de Bruxelles Capitale, Brussels, Belgium, and by GENomic profiling of Gastrointestinal Inflammatory-Sensitive CANcers ( GENGISCAN), Belgian FNRS PDR (T100914F to G.B.). Funding for open access charge: São Paulo Research Foundation (FAPESP) (2015/07925-5).