Anchored to the Gene: Sketching topograpHi-C maps of the Genome

Tourtellotte, Jocelyn

Etd

Anchored to the Gene: Sketching topograpHi-C maps of the Genome

Pubblico Deposited

The identity of each cell is defined by the genes it expresses, which is predicated by the three- and four-dimensional organization of chromatin in the nucleus. The nuclear pore complex (NPC) guides such gene expression by physically interacting with cell-type specific genes combinations. These genes are identifiable by DamID-fused nucleoporin, making the NPC a physical reference point. Guided by these nuclear waypoints, Hi-C data can be integrated to further models for organization of the genome at the nuclear periphery. For biological and computational reasons, analyzing Hi-C data is most effective for examining interactions between regions on the same chromosome – cis-interactions. Accordingly, visualization methods primarily focused on what is happening “along the diagonal”. We propose using kernel density estimation, a method frequently applied in ecology and epidemiology, as a chromosome-agnostic method for quantifying the probability of observing interactions at the “local” (gene) level. Subsequently, these densities are used to create contour plots that depict the regions most likely interaction along the respective lengths of the pair. Although such a targeted approach is not unique in the realm of chromatin capture as a whole – there exist targeted applications of such techniques – by its nature Hi-C data lends itself to a “global” perspective. Therefore, a framework for a “local” approach to Hi-C data analysis was constructed in conjunction with expanding our visualization toolbox. This framework will be used to integrate additional data-types and guide microscopy-based research of genome organization at the nuclear periphery.

Creator