HiCInterpolate: 4D Spatiotemporal Interpolation of Hi-C Data for Genome Architecture Analysis.

Motivation: Studying the three-dimensional (3D) structure of a genome, including chromatin loops and Topologically Associating Domains (TADs), is essential for understanding how the genome is organized, such as gene activation, cell development, protein-protein interaction, etc. Hi-C protocol enables us to study 3D genome structure and organization. Chromatin 3D structure changes dynamically over time, and modeling these continuous changes is crucial for downstream analysis in various domains such as disease diagnosis, vaccine development, etc. The high expense and impracticality of continuous genome sequencing, particularly what evolves between two timestamps, limit the most effective genomic analysis. It is crucial to develop a straightforward and cost-efficient method for constantly generating genomic data between two timestamps in order to address these constraints. Results: In this study, we developed HiCInterpolate, a 4D spatiotemporal interpolation architecture that accepts two timestamp Hi-C contact matrices to interpolate intermediate Hi-C contact matrices at high resolution. HiCInterpolate predicts the intermediate Hi-C contact map using a deep learning-based flow predictor, and a feature encoder and decoder architecture similar to U-Net. In addition, HiCInterpolate supports downstream analysis of multiple 3D genomic features, including A/B compartments, chromatin loops, TADs, and 3D genome structure, through an integrated analysis pipeline. Across multiple evaluation metrics, including PSNR, SSIM, GenomeDISCO, HiCRep, and LPIPS, HiCInterpolate achieved consistently strong performance. Biological validation further demonstrated preservation of key chromatin organization features, such as chromatin loops, A/B compartments, and TADs. Together, these results indicate that HiCInterpolate provides a robust computer vision-based framework for high-resolution interpolation of intermediate Hi-C contact matrices and facilitates biologically meaningful downstream analyses. Availability: HiCInterpolate is publicly available at https://github.com/OluwadareLab/HiCInterpolate.