A method for chromatin domain partitioning based on hypergraph clustering

Abstract

For many years, multi-scale models of chromatin domains, such as A/B compartments, sub-compartments, topologically associated domains (TADs), sub-TADs, and loops have been popular. However, existing methods can only identify structures at a single scale and cannot partition multi-scale structures. In this paper, we proposed a method (TORNADOES) for chromatin domain partitioning based on hypergraph clustering. First, we use a density clustering algorithm to identify TADs at different scales based on Hi-C data with different resolutions. Then, by combining ChIP-seq data features and TAD results at different scales, we generate a hypergraph based on these TADs. Finally, we partition the chromatin domain structure at different scales, including A/B, A1, A2, B1, B2, and B3 based on the Laplacian matrix feature of the hypergraph. Similarity comparison experiments and ChIP-seq signal enrichment analysis are performed on the A/B region and sub-TAD levels, respectively, demonstrating that our method can identify chromatin domains with distinct features and provide a deeper understanding of the organizational patterns and functional differences in TADs at the genomic hierarchical structure. Comparative analysis of multiple cell line data shows that TORNADOES can better classify different numbers and types of compartments by changing the factors ChIP-seq data and clustering number used to characterize TAD compared to other methods. Source code for the TORNADOES method can be found at https://github.com/ghaiyan/TORNADOES.

Keywords

• Hi-C
• A/B compartment
• Sub-compartment
• Hypergraph generation
• Hypergraph clustering