Computational Enhanced Hi-C data reveals the function of structural geometry in genomic regulation

Abstract

High-throughput chromosome conformation capture (Hi-C) technique profiles the genomic structure in a genome-wide fashion. The reproducibility and consistency of Hi-C data are essential in characterizing dynamics of genomic structures. We developed a diffusion-based method, CTG (Hi-C To Geometry), to deal with the technical bias induced by insufficient sampling in sequencing and obtain reliable gemeotric information of the chromatin. CTG properly quantifies dubiously weak or even undetected interactions and produces a consistent and reproducible framework for the 3D genomic structure. CTG allows for a reliable genome-wide insight on the alteration of genomic structures under different cellular conditions and reveals correlations between genomic-proximal genes at both transcriptional and translational levels. Cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as that with the transcription correlation reveals the coordinated inter-molecular structural and regulatory information passage in the central dogma.

Characterization of network hierarchy reflects cell-state specificity in genome organization

“…With these annotated functional contacts acting as bridging edges, chromatin functions as a complex dynamic network transmitting signals vital for cell viability. The correspondence of chromatin-fragment interaction and the protein-protein interaction demonstrated that 3D genome contributes to protein interactome which directly exercises biological functions 22,23 . In addition, noncoding loci without any annotations are indispensable for stability of chromatin structure and maintaining cell identities, i.e., targeted deletion of chromatin loci close to many loci in space can computationally impose the network structural property of a cancer cell onto a normal cell 12 .…”

Characterization of network hierarchy reflects cell state specificity in genome organization

“…Genome architecture plays an important role in transcription regulation ( Liu et al 2018 ; Deng et al 2022 ; He et al 2022 ). Instead of maintaining a static configuration, chromatin structure is dynamic ( Barth et al 2020 ).…”