Using GARDEN-NET and ChAseR to explore human haematopoietic 3D chromatin interaction networks

We introduce an R package and a web-based visualization tool for the representation, analysis and integration of epigenomic data in the context of 3D chromatin interaction networks. GARDEN-NET allows for the projection of user-submitted genomic features on pre-loaded chromatin interaction networks, exploiting the functionalities of the ChAseR package to explore the features in combination with chromatin network topology properties. We demonstrate the approach using published epigenomic and chromatin structure datasets in haematopoietic cells, including a collection of gene expression, DNA methylation and histone modifications data in primary healthy myeloid cells from hundreds of individuals. These datasets allow us to test the robustness of chromatin assortativity, which highlights which epigenomic features, alone or in combination, are more strongly associated with 3D genome architecture. We find evidence for genomic regions with specific histone modifications, DNA methylation, and gene expression levels to be forming preferential contacts in 3D nuclear space, to a different extent depending on the cell type and lineage. Finally, we examine replication timing data and find it to be the genomic feature most strongly associated with overall 3D chromatin organization at multiple scales, consistent with previous results from the literature. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.INSERM; Fondation Toulouse Cancer Santé and Pierre Fabre Research Institute as part of the Chair of Bioinformatics in Oncology of the CRCT [to M.M., V.P.]; BioInfo4Women programme at the Barcelona Supercomputing Center [to V.P.]; N.C. acknowledges an Internship scholarship from University of Science and Technology of Hanoi, Vietnam; Spanish Ministry of Economy, Industry and Competitiveness (MEIC) through the Instituto de Salud Carlos III and the 2014–2020 Smart Growth Operating Program [to E.R.]; EMBL partnership and co-financing with the European Regional Development Fund (MINECO/FEDER) [BIO2015-71792-P to E.R.]; Centro de Excelencia Severo Ochoa, and the Generalitat de Catalunya through the Departament de Salut, Departament d’Empresa i Coneixement and the CERCA Programme [to E.R.]; Plan Nacional [PGC2018-099640-B-I00 to E.R.]. Funding for open access charge: Chair of Bioinformatics in Oncology of the CRCT [to V.P.].Peer ReviewedPostprint (published version