Networks based approaches in epigenomics, evolution and biomedicine
Network biology, a growing field of Computational Biology, opens great new possibilities for the study of complex biological systems. In this presentation, I will review four specific cases of the application network approaches.
In the first study, we processed heterogeneous ChIP-Seq information to build a comprehensive genome co-localization network of Chromatin Related Proteins (CRPs), histone marks and DNA modifications in mouse embryonic stems cells. In this network, co-localization preferences can be translated into specific of “mESC Chromatin States”, such as active regions or enhancers. The study of the properties of the “co-localization” network points to the 5hmC DNA modifications, as the key component in the organization of the mouseESC network.
In a second network based study, the importance of 5hmC, as organizer of the epigenetic network, is reinforced by the evolutionary analysis of the protein components of the network. There, 5hmC acts as a mediator in the co-evolution of the CRPs protein components of the mESC network.
The third network-based approach explores the functional significance of the mESC Epigenetic Properties and Chromatin States, by analysing them in the context of the structure of the chromatin in the cell nucleus. The results revealed interesting properties of the organization of the mESC epigenetic control system, in line with the emerging models of gene expression control and chromatin organization, and again support the role of 5hmC as a factor present in a significant number of interactions related with active transcription in mouse embryonic stems cells.
One final network approach shows how the network properties can help to understand the complex relations between human diseases based on gene expression levels, in a large scale network connecting pairs of patients with a significant overlap between gene expression profiles.
Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin
Network of ESCs. Perner et al., (2016) Cell Rep. http://www.cell.com/cell-reports/pdf/S2211-1247(16)00028-0.pdf Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity. Pancaldi et al., (2016) Genome Biol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939006/
The direct and invers comorbidity network. Sanchez-Valle, Pancaldi, Valencia, 2018 in preparation.
Parts of this work were developed in collaboration with: Vingron's (MPIMG, Berlin), Fraser’s (Babraham Institute), and Baudot’s labs (CNRS, Marseille)
ICREA Professor, LIFE SCIENCES DEPARTMENT DIRECTOR
BSC Barcelona Supercomputing Center
Computational Systems Biology of Cancer Team
Directeur de l'U900