Introduction

Cancer development and progression is driven by a complex pattern of genomic and epigenomic perturbations. Both types of perturbations can affect gene expression levels and disease outcome. Integrative analysis of cancer genomics data may therefore improve detection of perturbed genes and prediction of disease state. As different data types are usually dependent, analysis based on independence assumptions will make inefficient use of the data and potentially lead to false conclusions.Here, we present PINCAGE (Probabilistic INtegration of CAncer GEnomics data), a method that uses probabilistic integration of cancer genomics data for combined evaluation of RNA-seq gene expression and 450k array DNA methylation measurements of promoters as well as gene bodies. It models the dependence between expression and methylation using modular graphical models, which also allows future inclusion of additional data types.We apply our approach to a Breast Invasive Carcinoma dataset from The Cancer Genome Atlas consortium, which includes 82 adjacent normal and 730 cancer samples. We identify new biomarker candidates of breast cancer development (PTF1A, RABIF, RAG1AP1, TIMM17A, LOC148145) and progression (SERPINE3, ZNF706). PINCAGE discriminates better between normal and tumour tissue and between progressing and non-progressing tumours in comparison with established methods that assume independence between tested data types, especially when using evidence from multiple genes. Our method can be applied to any type of cancer or, more generally, to any genomic disease for which sufficient amount of molecular data is available.R scripts available at http://moma.ki.au.dk/prj/pincage/: michal.switnicki@clin.au.dk or jakob.skou@clin.au.dkSupplementary data are available at Bioinformatics online.

Publications

  1. PINCAGE: probabilistic integration of cancer genomics data for perturbed gene identification and sample classification.
    Cite this
    Świtnicki MP, Juul M, Madsen T, Sørensen KD, Pedersen JS, 2016-05-01 - Bioinformatics (Oxford, England)

Credits

  1. Michał P Świtnicki
    Developer

  2. Malene Juul
    Developer

  3. Tobias Madsen
    Developer

  4. Karina D Sørensen
    Developer

  5. Jakob S Pedersen
    Investigator

    Department of Molecular Medicine (MOMA) Bioinformatics Research Centre (BiRC), Aarhus University, Denmark

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Summary
AccessionBT000106
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesR
User InterfaceTerminal Command Line
Download Count0
Country/RegionDenmark
Submitted ByJakob S Pedersen