Uncovering the statistical physics of 3D chromosomal organization using data-driven modeling.

Curr Opin Struct Biol

Center for Theoretical Biological Physics, Rice University, Houston, TX, USA; Department of Physics and Astronomy, Rice University, Houston, TX, USA; Department of Chemistry, Rice University, Houston, TX, USA; Department of Biosciences, Rice University, Houston, TX, USA. Electronic address:

Published: August 2022

AI Article Synopsis

  • Recent advancements have focused on understanding how the 3D organization of the genome affects its function, driven by techniques like Hi-C that combine DNA proximity ligation with high-throughput sequencing.
  • These methods have led to the need for theoretical models to interpret the complex data, resulting in the development of 3D polymer models that explain the physical mechanisms of genome architecture.
  • Two noteworthy models, the minimal chromatin model (MiChroM) and the maximum entropy genomic annotations from biomarkers (MEGABASE), have shown significant success in accurately reflecting chromosomal structures based on Hi-C and DNA-tracing data.

Article Abstract

In recent years, much effort has been devoted to understanding the three-dimensional (3D) organization of the genome and how genomic structure mediates nuclear function. The development of experimental techniques that combine DNA proximity ligation with high-throughput sequencing, such as Hi-C, have substantially improved our knowledge about chromatin organization. Numerous experimental advancements, not only utilizing DNA proximity ligation but also high-resolution genome imaging (DNA tracing), have required theoretical modeling to determine the structural ensembles consistent with such data. These 3D polymer models of the genome provide an understanding of the physical mechanisms governing genome architecture. Here, we present an overview of the recent advances in modeling the ensemble of 3D chromosomal structures by employing the maximum entropy approach combined with polymer physics. Particularly, we discuss the minimal chromatin model (MiChroM) along with the "maximum entropy genomic annotations from biomarkers associated with structural ensembles" (MEGABASE) model, which have been remarkably successful in the accurate modeling of chromosomes consistent with both Hi-C and DNA-tracing data.

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http://dx.doi.org/10.1016/j.sbi.2022.102418DOI Listing

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