A Computational Approach to Demonstrate the Control of Gene Expression via Chromosomal Access in Colorectal Cancer

Abstract

Background: Improved technologies for chromatin accessibility sequencing such as ATAC-seq have increased our understanding of gene regulation mechanisms, particularly in disease conditions such as cancer. Methods: This study introduces a computational tool that quantifies and establishes connections between chromatin accessibility, transcription factor binding, transcription factor mutations, and gene expression using publicly available colorectal cancer data. The tool has been packaged using a workflow management system to allow biologists and researchers to reproduce the results of this study. Results: We present compelling evidence linking chromatin accessibility to gene expression, with particular emphasis on SNP mutations and the accessibility of transcription factor genes. Furthermore, we have identified significant upregulation of key transcription factor interactions in colon cancer patients, including the apoptotic regulation facilitated by E2F1, MYC, and MYCN, as well as activation of the BCL-2 protein family facilitated by TP73. Conclusion: This study demonstrates the effectiveness of the computational tool in linking chromatin accessibility to gene expression and highlights significant transcription factor interactions in colorectal cancer. The code for this project is openly available on GitHub.

Keywords

• colorectal cancer
• epigenetics
• chromatin accessibility
• snakemake