Jeroen de Ridder
Mapping multi-contact chromatin interactions on the MinION
About Jeroen de Ridder
Dr. de Ridder is Principle Investigator / Associate professor in Bioinformatics. His lab specializes in creating novel computational strategies and algorithms that transform, normalize, integrate and mine large volumes of data. Much of his research floats on machine learning approaches. His recent work has focussed on computational approaches to map chromatin interactions using long-read sequencing platforms.
Allahyar, A. et al. Locus-Specific Enhancer Hubs And Architectural Loop Collisions Uncovered From Single Allele DNA Topologies. bioRxiv 206094 (2017). doi:10.1101/206094
Chromatin folding is increasingly recognized as a regulator of genomic processes such as gene activity. Chromosome conformation capture (3C) methods have been developed to unravel genome topology through the analysis of pair-wise chromatin contacts and have identified many genes and regulatory sequences that, in populations of cells, are engaged in multiple DNA interactions. However, pair-wise methods cannot discern whether contacts occur simultaneously or in competition on the individual chromosome. We present a novel 3C method, Multi-Contact 4C (MC-4C), that applies nanopore sequencing to study multi-way DNA conformations of tens of thousands of individual alleles for distinction between cooperative, random and competing interactions. MC-4C can uncover previously missed structures in sub-populations of cells. It reveals unanticipated cooperative clustering between regulatory chromatin loops, anchored by enhancers and gene promoters, and CTCF and cohesin-bound architectural loops.
Jeroen de Ridder