XCI

XCI reconstructs and models the three-dimensional (3D) structure of the X-chromosome during X-chromosome inactivation using a cubic lattice and population Hi-C data to infer structural changes associated with Xist lncRNA spreading.

Key Features:

• Lattice-Based Modeling: Utilizes a 3D cubic lattice to simulate and store DNA bead chains representing chromosomes for structural reconstruction.
• Population Hi-C Integration: Employs population Hi-C data from both active and inactive X-chromosomes to computationally reconstruct 3D architecture, addressing the absence of direct Hi-C measurements during XCI.
• Xist lncRNA Influence: Incorporates the role of Xist long non-coding RNA and its localization to model structural changes induced during XCI.
• RAP Data Integration: Integrates RNA Polymerase Assay (RAP) data for Xist localization intensities to model dynamics of DNA bead pairs during inactivation.
• Zero-Value Modeling: Uses a 2D Gaussian function to model zero values in Hi-C contact matrices to represent spatial proximity information.
• Monte Carlo Optimization: Applies simulated annealing and Metropolis-Hastings simulations to generate initial and refined 3D structures.
• Temporal Reconstruction: Reconstructs 3D structures at defined time points (3 hours, 6 hours, and 24 hours) after Xist expression initiation.

Scientific Applications:

• Understanding Chromosome Dynamics: Provides insights into structural changes of the X-chromosome during inactivation and mechanisms of dosage compensation.
• Gene Regulation Studies: Facilitates investigation of how spatial genome organization and Xist-mediated structural changes influence gene expression during XCI.

Methodology:

Models zero entries in Hi-C contact matrices with a 2D Gaussian function; generates 3D structures using simulated annealing and Metropolis-Hastings simulations; integrates RAP-derived Xist localization intensities to model DNA bead-pair dynamics; reconstructs structures at 3 h, 6 h, and 24 h post-Xist induction.