Inferring Spatial Organization of Individual Topologically Associated Domains via Piecewise Helical Model.

The recently developed Hi-C technology enables a genome-wide view of chromosome spatial organizations, and has shed deep insights into genome structure and genome function. However, multiple sources of uncertainties make downstream data analysis and interpretation challenging. Specifically, statistical models for inferring three-dimensional (3D) chromosomal structure from Hi-C data are far from their maturity. Most existing methods are highly over-parameterized, lacking clear interpretations, and sensitive to outliers. In this study, we propose a parsimonious, easy to interpret, and robust piecewise helical model for the inference of 3D chromosomal structure of individual topologically associated domain from Hi-C data. When applied to a real Hi-C dataset, the piecewise helical model not only achieves much better model fitting than existing models, but also reveals that geometric properties of chromatin spatial organization are closely related to genome function.