Identification of Specific Gene Modules and Candidate Signatures in Necrotizing Enterocolitis Disease: Ne1twork-based Gene Co-expression Approach

Abstract

Necrotizing enterocolitis (NEC) is a serious disease of the gastrointestinal systems that primarily affects premature newborns' intestine in neonatal intensive care units. The present study aimed to detect NEC molecular signatures and pathways from comprehensive bioinformatics analysis of NEC's RNA-seq transcriptomics. We performed systems biology analysis of RNA-seq transcriptomics data (with accession GSE64801) of NEC from nine NEC and five healthy controls. Differential expression of gene expression was performed using a combination of three R packages "DESeq2", "edgeR", “edger robust”. Gene co-expression analysis was performed using a weighted WGCNA package to identify gene modules, Gene Ontology (GO), pathway analysis, protein-protein interaction, gene-transcription factor, and gene-microRNA interaction analysis was performed. The differential expression analysis identified 966 differentially expressed genes (DEGs) in NEC from the RNA-seq dataset related to corresponding controls. The WGCNA showed the presence of three key gene modules. The GO analysis showed genes are enriched in metabolic processes, regulation of immune response and immune systems, cell communication, and cellular process. The immune and complement pathways are related to co-expressed key modules that were detected. The protein-protein interactions analysis showed the presence of key hub genes related to the modules. Integration of these co-expressed gene modules with regulatory networks showed the presence of significant key transcription factors and microRNAs as hub molecules. The present study's findings suggested the immune systems and complement cascade are key mechanisms of NEC pathogenesis. The comprehensive network analysis showed several key hub molecules that might be potential biomarkers and drug targets in NEC.