Finding unique patterns in transcriptome and epigenome of cancer cells

Abstract

Background: Studying Chromatin Architecture is paramount to an understanding of cells or nuclei in disease and normal state. With recent advances in genomic technologies and computational power, new domains like Topologically associated domains (TAD) have been discovered. Studying TAD in the context of cancer cells gives insights into how chromatin folding relates to the survival of the patient. Exploiting chromatin interactions from the lens of enhancer-gene interactions is of cardinal value since identifying specific chromatin interactions (enhancer-gene pairs) in disease state cells which are etiology pairs for the disease, and using genomic editing technologies to knockdown these pairs, could be a potential precise and accurate model to beat disease cells, especially cancer cells. Our study is divided into two parts; in the first part, we build a method to understand TAD biology and its implication in estimating patient survival. In the second part of our study, we modified a previously proposed method scEChiA to detect enhancer-gene pairs interactions in cancer-specific cells using RNA-seq profiles. We further validates the predicted interactions with 4D genome2 and Activity by Contact (ABC) databases Results: We identified TAD chr1_171750000_172350000 in Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) cancer type, which according to our curated algorithms and pipelines is found to be the most survival TAD with high survival score. We explored this TAD biology of how genes in this TAD interplay with each other creating a network that ultimately defines this TAD property. From the scEChiA R package, we identified several enhancer- 8 enhancer, enhancer-gene, and gene-gene interaction pairs in chromosome 11 of Diffuse large B cell lymphoma (DLBCL) cancer type, which was benchmarked with 4D genome and Activity by contact chromatin interaction databases. Conclusion: Identification of specific TAD, which is most surviving in cancer cell lines, and understanding its underlying biology gives a new definition of TAD property and function. Chromatin interaction results from scEChiA along pipelined developed algorithms give enhancer-gene, enhancer-enhancer, and gene-gene interactions, which could be a database for potential target whose knockdown could be a potential cure to cancer cells.