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

Area of Science:

• Genomics and Bioinformatics
• Epigenetics
• Systems Biology

Background:

• Chromatin accessibility sequencing (e.g., ATAC-seq) is crucial for understanding gene regulation and networks.
• Integrating large-scale accessibility datasets is challenging due to fragmented tools focusing on preprocessing.
• A comprehensive end-to-end solution is needed for both preprocessing and downstream analysis of epigenomic data.

Purpose of the Study:

• To introduce cisDynet, a holistic computational solution for streamlined chromatin accessibility data analysis.
• To provide a user-friendly platform for both basic and advanced downstream analyses of epigenomic data.
• To facilitate the integration of diverse epigenomic datasets and enhance the discovery of regulatory mechanisms.

Main Methods:

• Developed cisDynet, integrating Snakemake and R for efficient data preprocessing.
• Implemented advanced downstream analysis modules including peak annotation, differential analysis, motif enrichment, and network construction.
• Applied cisDynet to ENCODE ATAC-seq data and mouse embryonic development time-course data.

Main Results:

• cisDynet successfully delineated tissue-specific open chromatin regions (OCRs) and linked them to genes.
• The tool enabled enrichment analysis of 1861 genome-wide association study (GWAS) variants with OCRs.
• Analysis of time-course data revealed dynamic OCR behavior and identified key transcription factors in mouse development.

Conclusions:

• cisDynet provides a user-friendly, reproducible solution for comprehensive epigenomic data exploration.
• The platform simplifies complex analyses, reducing the need for extensive coding.
• cisDynet enhances the ability to uncover genetic regulatory mechanisms and construct gene regulatory networks.