cisDynet: an integrated platform for modeling gene-regulatory dynamics and networks

Abstract

Chromatin accessibility sequencing has been widely used for uncovering genetic regulatory mechanisms and inferring gene regulatory networks. However, effectively integrating large-scale chromatin accessibility datasets has posed a significant challenge. This is due to the lack of a comprehensive end-to-end solution, as many existing tools primarily emphasize data pre-processing and overlook downstream analyses. To bridge this gap, we have introduced cisDynet, a holistic solution that combines streamlined data pre-processing using Snakemake and R functions with advanced downstream analysis capabilities. cisDynet excels in conventional data analyses, encompassing peak statistics, peak annotation, differential analysis, motif enrichment analysis and more. Additionally, it allows to perform sophisticated data exploration such as tissue-specific peak identification, time-course data fitting, integration of RNA-seq data to establish peak-to-gene associations, constructing regulatory networks, and conducting enrichment analysis of GWAS variants. As a proof of concept, we applied cisDynet to re-analyze the comprehensive ATAC-seq datasets across various tissues from the ENCODE project. The analysis successfully delineated tissue-specific open chromatin regions (OCRs), established connections between OCRs and target genes, and effectively linked these discoveries with 1,861 GWAS variants. Furthermore, cisDynet was instrumental in dissecting the time-course open chromatin data of mouse embryonic development, revealing the dynamic behavior of OCRs over time and identifying key transcription factors governing differentiation trajectories. In summary, cisDynet offers researchers a user-friendly solution that minimizes the need for extensive coding, ensures the reproducibility of results, and greatly simplifies the exploration of epigenomic data. Graphical AbstractcisDynet enables the exploration of the cis-regulatory chromatin dynamics and networks. It offers a streamlined preprocessing pipeline built on Snakemake, along with an R package for advanced downstream data analysis and visualization. It is free to access on GitHub (https://github.com/tzhu-bio/cisDynet). HighlightsO_LIThe cisDynet enables comprehensive and efficient processing of chromatin accessibility data, including pre-processing, advanced downstream data analysis and visualization. C_LIO_LIcisDynet provides a range of analytical features such as processing of time course data, co-accessibility analysis, linking OCRs to genes, building regulatory networks, and GWAS variant enrichment analysis. C_LIO_LIcisDynet simplifies the identification of tissue/cell type-specific OCRs or dynamic OCR changes over time and facilitates the integration of RNA-seq data to depict temporal trajectories. C_LI