Three-dimensional genomics

Li Li, Cheng Peng

In the last decade, next-generation sequencing (NGS) as a powerful high-throughput genome wide tool has been introduced to various aspects of molecular biology and brings it to the era of big data as a driving force. Three-dimensional (3D) genomics, which study the spatial and dynamic architecture and organization of chromosomes in living cells, is among the areas which has revealed a lot of discoveries and insights using NGS-derived technologies. Our research is in this fast-growing area of 3D genomics, especially focused on analyzing high-throughput chromatin interaction data generated by NGS. We use statistical models and other machine learning methods to analyze chromatin interaction data from various species. Specifically, we build integrated models by taking into account both artefacts induced by experiments and signals which are indicative of genome structure hierarchy including compartments, TADs and loops. Genome architecture is not a static state, but a structure organized and adapted for dynamic functions. By applying 3D genomics and other NGS technologies, we also study biological processes including cell reprogramming, cell differentiation and tissue specificity. Cells as populations in organisms show a lot of cell to cell variation. Traditional Hi-C only give a picture of cell ensemble. Chromosome architecture mechanism and dynamics can be better understood in scenario of single cells. Thus, we also seek to develop tools for processing and analyzing other emerging Hi-C-derived technologies, including single cell Hi-C and SMRT Hi-C.

Keywords: Hi-C; Three-dimensional genomics; TADs; Epigenetics

Rowley, M.J., and Corces, V.G. (2018). Organizational principles of 3D genome architecture. Nature Reviews Genetics.