Chromosome Modeling on Downsampled Hi-C Maps Enhances the Compartmentalization Signal

Author(s)

Oliveira, Jr., Antonio B. ^[1] ; Estrada, Cynthia Perez ^{[2, 1]} ; Aiden, Erez Lieberman ^{[2, 1]} ; Contessoto, Vinicius G. ^{[1, 3]} ; Onuchic, Jose N. ^{[4, 5]}

Affiliation

^[1] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77251 - USA

^[2] Baylor Coll Med, Ctr Genome Architecture, Dept Mol & Human Genet, Houston, TX 77030 - USA

^[3] UNESP Univ Estadual Paulista, Inst Biociencias Letras & Crencias Exatas, Dept Fis, Sao Jose Do Rio Preto, SP - Brazil

^[4] Rice Univ, Dept Phys & Astron, Ctr Theoret Biol Phys, Dept Chem, Houston, TX 77251 - USA

^[5] Rice Univ, Dept Biosci, Houston, TX 77251 - USA

• Document type: Journal article
• Source: Journal of Physical Chemistry B; v. 125, n. 31, p. 8757-8767, AUG 12 2021.
• Web of Science Citations: 0

Abstract

The human genome is organized within a nucleus where chromosomes fold into an ensemble of different conformations. Chromosome conformation capture techniques such as Hi-C provide information about the genome architecture by creating a 2D heat map. Initially, Hi-C map experiments were performed in human interphase cell lines. Recently, efforts were expanded to several different organisms, cell lines, tissues, and cell cycle phases where obtaining high-quality maps is challenging. Poor sampled Hi-C maps present high sparse matrices where compartments located far from the main diagonal are difficult to observe. Aided by recently developed models for chromatin folding and dynamics investigation, we introduce a framework to enhance the compartments' information far from the diagonal observed in experimental sparse matrices. The simulations were performed using the Open-MiChroM platform aided by new trained parameters in the minimal chromatin model (MiChroM) energy function. The simulations optimized on a downsampled experimental map (10% of the original data) allow the prediction of a contact frequency similar to that of the complete (100%) experimental Hi-C. The modeling results open a discussion on how simulations and modeling can increase the statistics and help fill in some Hi-C regions not captured by poor sampling experiments. Open-MiChroM simulations allow us to explore the 3D genome organization of different organisms, cell lines, and cell phases that often do not produce high-quality Hi-C maps. (AU)

• FAPESP's process: 16/13998-8 - Rational evolution by computational methods applied to predict mutations in enzymes to biofuels production
• Grantee: Vinícius de Godoi Contessoto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/09662-7 - Rational Evolution by Computational Methods Applied in Enzymes Related to Bioethanol Production
• Grantee: Vinícius de Godoi Contessoto
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor