AN INTEGRATIVE OMICS APPROACH ON GENE REGULATORY NETWORKS GOVERNING STEM CELL DIFFERENTIATION

Abstract

The process of stem cell differentiation is highly regulated and involves the intricate interaction of genes, transcription factors, epigenetic modifications, proteins, and non-coding RNAs. The study of these regulatory mechanisms is of critical importance to the future of regenerative medicine, disease modeling and cell-based therapeutics. The paper suggests an integrative omics model of the reconstruction of gene regulatory networks (GRNs) that regulate stem cell differentiation by integrating transcriptomic, epigenomic, proteomic and miRNA expression data. The suggested methodology uses full data pre-treatment, feature monadic, multi-omics combination, and regulatory communication to make a single expression of molecular processes participating in cellular differentiation. This is followed by reconstruction of a gene regulatory network to determine the important regulatory interactions and vital hub genes that drive lineage commitment and development programs. To determine the biological meaning of the regulatory modules identified, functional enrichment analysis with the help of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways is conducted. The efficacy of the suggested framework is assessed through typical measures of network reconstructions such as Precision, Recall, F1-Score, Area Under the Receiver Operating Characteristic Curve (AUROC), Area Under the Precision Recall Curve (AUPRC), and Matthews Correlation Coefficient (MCC). Through experimental findings, it is shown that integrating multiple layers of omics greatly enhances the discovery of biologically meaningful regulatory interactions relative to traditional, single-omics methods. The rebuilt networks demonstrate some important hub genes and differentiation-related pathways that are pivotal in the determination of stem cell fate. Altogether, the suggested integrative omics methodology offers a very strong and biologically understandable model of explaining gene regulatory processes controlling stem cell differentiation and has a great potential in further regenerative medicine studies.