(306h) Computational Recovery of Chromatin Conformations From Experimental Contact Probabilities

Chromatin is a nanoscale fiber resulting from the self-assembly of DNA and proteins within the nucleus of eukaryotic cells. The conformation of this fiber is believed to play a role in the regulation of essential cellular processes, such as DNA transcription, replication, recombination, and repair. However, the spatial organization of chromatin and its functional implications are not yet well understood. Here we present computational methods that can be used to determine chromatin conformations by analyzing DNA sequences obtained from high-throughput chromosome conformation capture (Hi-C) experiments. We use the DNA sequences to infer the probability of contact between different parts of chromatin in vivo. We then process these contact probabilities to recover possible ensembles of chromatin conformation, which can be further analyzed to correlate spatial properties with gene activity. We validate our computational methods against simulations of both Hi-C experiments and a coarse-grained polymer model representing the 30-nm chromatin fiber. We also compare computational predictions to results of fluorescence in situ hybridization (FISH) experiments. Our methods provide a means to deduce and compare the spatial organization of chromatin in different cell types, thus elucidating the interplay between chromatin organization and cellular processes.