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Inference of chromosome 3D structures from GAM data by a physics computational approach

Authors

  • L. Fiorillo
  • S. Bianco
  • A.M. Chiariello
  • M. Barbieri
  • A. Esposito
  • C. Annunziatella
  • M. Conte
  • A. Corrado
  • A. Prisco
  • A. Pombo
  • M. Nicodemi

Journal

  • Methods

Citation

  • Methods

Abstract

  • The combination of modelling and experimental advances can provide deep insights for understanding chromatin 3D organization and ultimately its underlying mechanisms. In particular, models of polymer physics can help comprehend the complexity of genomic contact maps, as those emerging from technologies such as Hi-C, GAM or SPRITE. Here we discuss a method to reconstruct 3D structures from Genome Architecture Mapping (GAM) data, based on PRISMR, a computational approach introduced to find the minimal polymer model best describing Hi-C input data from only polymer physics. After recapitulating the PRISMR procedure, we describe how we extended it for treating GAM data. We successfully test the method on a 6Mb region around the Sox9 gene and, at a lower resolution, on the whole chromosome 7 in mouse embryonic stem cells. The PRISMR derived 3D structures from GAM co-segregation data are finally validated against independent Hi-C contact maps. The method results to be versatile and robust, hinting that it can be similarly applied to different experimental data, such as SPRITE or microscopy distance data.


DOI

doi:10.1016/j.ymeth.2019.09.018