Strategies of Integrated Analysis of ATAC-seq and RNA-seq Data

The ATAC-seq and RNA-seq have been widely used in the epigenomes analysis of mammals. However, there is a lack of comprehensive integrated analysis of ATAC-seq and RNA-seq data. Here, we explored two effective strategies for analyzing ATAC-seq and RNA-seq data using proliferation and differentiation myoblast cells as model. One strategy is a joint analysis by integrating Hi-C data with ATAC-seq and RNA-seq data. The other strategy is to investigate the association between ATAC-seq and RNA-seq data only based on genome physical distance in the case of no availability of Hi-C data. Hi-C data-based integrated analysis showed a strong correlation between genes and distal enhancers, particularly between genes and promoters, within the topologically associated domains (TADs) and chromatin loops. In the absence of Hi-C data, the integrated analysis based on 500 kb physical distance between genes and associated peaks revealed a strong positive correlation between gene expression and chromatin accessibility. Moreover, the function enrichment analysis indicated that both integrated analysis results could reflect the cellular states. Our proposed two integrated analysis strategies combine ATAC-seq and RNA-seq data, which lay a foundation for subsequent epigenetics studies.