Bioinformatic Multi-Strategy Profiling of Congenital Heart Defects for Molecular Mechanism Recognition

Congenital heart defects (CHDs) rank among the most common birth defects, presenting diverse phenotypes. Genetic and environmental factors are critical in molding the process of cardiogenesis. However, these factors' interactions are not fully comprehended. Hence, this study aimed to identify and characterize differentially expressed genes involved in CHD development through bioinformatics pipelines. We analyzed experimental datasets available in genomic databases, using transcriptome, gene enrichment, and systems biology strategies. Network analysis based on genetic and phenotypic ontologies revealed that EP300, CALM3, and EGFR genes facilitate rapid information flow, while NOTCH1, TNNI3, and SMAD4 genes are significant mediators within the network. Differential gene expression (DGE) analysis identified 2513 genes across three study types, (1) Tetralogy of Fallot (ToF); (2) Hypoplastic Left Heart Syndrome (HLHS); and (3) Trisomy 21/CHD, with LYVE1, PLA2G2A, and SDR42E1 genes found in three of the six studies. Interaction networks between genes from ontology searches and the DGE analysis were evaluated, revealing interactions in ToF and HLHS groups, but none in Trisomy 21/CHD. Through enrichment analysis, we identified immune response and energy generation as some of the relevant ontologies. This integrative approach revealed genes not previously associated with CHD, along with their interactions and underlying biological processes.