Analysis of Genome Architecture Mapping Data with a Machine Learning and Polymer-Physics-Based Tool

Understanding the mechanisms driving the folding of chromosomes in nuclei is a major goal of modern Molecular Biology. Recent technological advances in microscopy (FISH, STORM) and sequencing approaches (Hi-C, GAM, SPRITE) enabled to collect quantitative data about chromatin 3D architecture, revealing a non-random and highly specific organization. To transform such tremendous amount of data into valuable insights on genome folding, heavy computational analyses are required. Here, we study the performances of PRISMR, a computational tool based on Machine Learning strategies and Polymer Physics principles, to explore genome 3D structure from Genome Architecture Mapping (GAM) data. Using such data, we show that PRISMR can successfully reconstruct the 3D structure of real genomic regions at various length scales, from mega-base sized loci to whole chromosomes. Importantly, the inferred structures are validated against independent Hi-C data. Finally, we show how PRISMR can be effectively employed to explore differences between experimental methods.