Biology subjects

Pop, R. T.

Publications and source records attributed to Pop, R. T..

3 recordsLinked to original sources

bioRxiv2024

Gene regulatory network integration with multi-omics data enhances survival predictions in cancer

The emergence of high-throughput omics technologies has resulted in their wide application to cancer studies, greatly increasing our understanding of the disruptions occurring at different molecular levels. The role of gene regulation as a core driver of biological processes and its role in the development and progression of cancer has been well established. Transcriptional regulation, a crucial aspect of gene regulation, can be represented as a network of interactions between regulators (such as transcription factors) and their target genes. These networks are known as gene regulatory networks (GRNs). Several joint dimensionality reduction (JDR) methods and tools for integrating multi-modal data have been developed in recent years. This study presents a new approach to integrate multi-modal data of different dimensions to consider sample-specific GRNs with multi-omics data in ten cancer datasets from The Cancer Genome Atlas (TCGA). We compare JDR models that include GRNs with those that do not, assessing their association with patient survival. We find that including GRNs can improve associations with patient survival across several cancer types. Focusing on liver cancer, our methodology identifies potential mechanisms of gene regulatory dysregulation associated with cancer progression.

systems biology↗

bioRxiv2023

Identification of mammalian transcription factors that bind to inaccessible chromatin

Transcription factors (TFs) are proteins that affect gene expression by binding to regulatory regions of DNA in a sequence specific manner. The binding of TFs to DNA is controlled by many factors, including the DNA sequence, concentration of TF, chromatin accessibility and co-factors. Here, we systematically investigated the binding mechanism of hundreds of TFs by analysing ChIP-seq data with our explainable statistical model, ChIPanalyser. This tool uses as inputs the DNA sequence binding motif; the capacity to distinguish between strong and weak binding sites; the concentration of TF; and chromatin accessibility. We asked whether TFs preferred to bind to DNA in open or dense chromatin conformation and found that approximately one third of TFs are predicted to bind the genome in a DNA accessibility independent fashion. Our model predicted this to be the case when the TF binds to its strongest binding regions in the genome, and only a small number of TFs have the capacity to bind dense chromatin at their weakest binding regions, such as CTCF USF2 and CEBPB. Our study demonstrated that the binding of hundreds of human and mouse TFs is predicted by ChIPanalyser with high accuracy and showed that many TFs can bind dense chromatin.

genomics↗

bioRxiv2023

Exposure to an enriched environment improves colonic epithelial barrier integrity and attenuates mouse experimental colitis by modulating a Myc-driven gene regulatory network

Withdrawal StatementThe authors have withdrawn their manuscript owing to erroneous labeling in two figures that have recently come to light. Experiments aiming to confirm the data presented are underway. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

immunology↗