Topological Data Analysis Reveals Principles of Chromosome Structure in Cellular Differentiation

Abstract

Topological data analysis (TDA) is a mathematically well-founded set of methods to derive robust information about the structure and topology of data. It has been applied successfully in several biological contexts. Derived primarily from algebraic topology, TDA rigorously identifies persistent features in complex data, making it well-suited to better understand the key features of three-dimensional chromosome structure. Chromosome structure has a significant influence in many diverse genomic processes and has recently been shown to relate to cellular differentiation. While there exist many methods to study specific substructures of chromosomes, we are still missing a global view of all geometric features of chromosomes. By applying TDA to the study of chromosome structure through differentiation across three cell lines, we provide insight into principles of chromosome folding and looping. We identify persistent connected components and one-dimensional topological features of chromosomes and characterize them across cell types and stages of differentiation. Availability: Scripts to reproduce the results from this study can be found at https://github.com/Kingsford-Group/hictda