Seminars-Computational strategies for the analysis of epigenetic landscape in cancer

EVENT : C3BI Seminars

Seminars-Computational strategies for the analysis of epigenetic landscape in cancer

Speaker : Valentina Boeva, Head of the Computational (Epi-)genetics of Cancer group – Institut Cochin (INSERM/CNRS), Paris Date : 08/09/2016 at 2:00 PM Location : Retrovirus room – LWOFF (22), Institut Pasteur, Paris

Computational strategies for the analysis of epigenetic landscape in cancer and their application to decipher rewiring of transcriptional regulatory networks in neuroblastoma.

Epigenetic landscape, i.e., positioning of diverse epigenetic marks along the genomic DNA, is known to evolve during tumor development and progression. For instance, as a consequence of specific genetic events (mutations or structural variants) or due to the general rewiring of the transcriptional regulatory networks, oncogenes often gain in cancer cells de novo active regulatory elements (enhancers and super-enhancers). Overexpression of certain components of repressive complexes (e.g., the EZH2 component of the Polycomb Repressive Complex 2) or mutations in genes coding for chromatin remodeling proteins (e.g., MLL2 and MLL3) can also result in epigenetic silencing of tumor suppressor genes or epigenetic activation of oncogenes. Thus, analysis of changes in the epigenetic landscape using the ChIP-seq technique can show extremely useful to get insights into the mechanisms of cancer development and progression.

In my talk, I will show how ChIP-seq data are used in cancer studies to assess changes of the epigenetic landscape. I will present methods we have developed in my group to normalize ChIP-seq signal and detect regions of enrichment in chromatin marks for datasets coming from cancer samples or identify regions of differential enrichment. Our methods account for copy number aberrations present in cancer genomes, different technical biases and variable signal-to-noise ratio between experiments. I will also present our unpublished results on the analysis of epigenetic profiles of 22 neuroblastoma cell lines and tumors, where we characterized the most potent de novo super-enhancers and associated them with neuroblastoma development via the process of rewiring of the core transcriptional regulatory networks.

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