Computer methods of analysis of chromosome contacts in the cell nucleus based on sequencing technology data

Abstract

The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research. The technique of chromatin immunoprecipitation and subsequent sequencing (ChIP-seq) make possible to determine binding sites of transcription factors that regulate expression of eukaryotic genes; genome transcription factors binding maps have been. The ChIA-PET technology allows exploring not only target protein binding sites, but also pairs of such sites on proximally located and interacting with each other chromosomes co-located in three-dimensional space of the cell nucleus. Here we discuss the principles of the construction of genomic maps and matrices of chromosome contacts according to ChIA-PET and Hi-C data that capture the chromosome conformation and overview existing software for 3D genome analysis including in house programs of gene location analysis in topological domains.