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bioRxiv · 10.1101/2024.01.10.574968

LoopSage: An Energy-Based Monte Carlo approach for the Loop Extrusion Modelling of Chromatin

Korsak, S.·Plewczynski, D.
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Abstract

The connection between the patterns observed in 3C-type experiments and the modeling of polymers remains unresolved. This paper presents a simulation pipeline that generates thermodynamic ensembles of 3D structures for topologically associated domain (TAD) regions by loop extrusion model (LEM). The simulations consist of two main components: a stochastic simulation phase, employing a Monte Carlo approach to simulate the binding positions of cohesins, and a dynamical simulation phase, utilizing these cohesins positions to create 3D structures. In this approach, the systems total energy is the combined result of the Monte Carlo energy and the molecular simulation energy, which are iteratively updated. The structural maintenance of chromosomes (SMC) protein complexes are represented as loop extruders, while the CCCTC-binding factor (CTCF) locations on DNA sequence are modeled as energy minima on the Monte Carlo energy landscape. Finally, the spatial distances between DNA segments from ChIA-PET experiments are compared with the computer simulations, and we observe significant Pearson correlations between predictions and the real data. LoopSage model offers a fresh perspective on chromatin loop dynamics, allowing us to observe phase transition between sparse and condensed states in chromatin.

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Korsak, S., Plewczynski, D.. 2024-01-12. LoopSage: An Energy-Based Monte Carlo approach for the Loop Extrusion Modelling of Chromatin. https://doi.org/10.1101/2024.01.10.574968

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