HiChew: a Tool for TAD Clustering in Embryogenesis

The three-dimensional structure of the Drosophila chromatin has been shown to change at the early stages of embryogenesis from the state with no local structures to compartmentalized chromatin segregated into topologically associated domains (TADs). However, the dynamics of TAD formation and its association with the expression and epigenetics dynamics is not fully understood. As TAD calling and analysis of TAD dynamics have no standard, universally accepted solution, we have developed HiChew, a specialized tool for segmentation of Hi-C maps into TADs of a given expected size and subsequent clustering of TADs based on their dynamics during the embryogenesis. To validate the approach, we demonstrate that HiChew clusters correlate with genomic and epigenetic characteristics. Particularly, in accordance with previous findings, the maturation rate of TADs is positively correlated with the number of housekeeping genes per TAD and negatively correlated with the length of housekeeping genes. We also report a high positive correlation of the maturation rate of TADs with the growth rate of the associated ATAC-Seq signal.