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Genetic and environmental factors are critical in molding the process of cardiogenesis. However, these factors\u2019 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.<\/jats:p>","DOI":"10.3390\/ijms252212052","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"12052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bioinformatic Multi-Strategy Profiling of Congenital Heart Defects for Molecular Mechanism Recognition"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-7518","authenticated-orcid":false,"given":"Fabyanne Guimar\u00e3es","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics and Evolution, Graduate Program in Genetics and Molecular Biology, Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil"},{"name":"Teratogen Information System (SIAT), Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Vitor Pacheco","family":"Foletto","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics and Evolution, Graduate Program in Genetics and Molecular Biology, Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil"},{"name":"Teratogen Information System (SIAT), Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"},{"name":"Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin Chaves Scimczak","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Teratogen Information System (SIAT), Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"},{"name":"Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-0460","authenticated-orcid":false,"given":"Lav\u00ednia","family":"Schuler-Faccini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics and Evolution, Graduate Program in Genetics and Molecular Biology, Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil"},{"name":"Teratogen Information System (SIAT), Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"},{"name":"National Institute on Population Medical Genetics (INAGEMP), Porto Alegre 90035-903, Brazil"},{"name":"Graduate Program in Children and Adolescent Health, Medicine Faculty, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-2272","authenticated-orcid":false,"given":"Thayne Woycinck","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics and Evolution, Graduate Program in Genetics and Molecular Biology, Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil"},{"name":"Teratogen Information System (SIAT), Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"},{"name":"Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"},{"name":"National Institute on Population Medical Genetics (INAGEMP), Porto Alegre 90035-903, Brazil"},{"name":"Bioinformatics Core, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil"},{"name":"Graduate Program in Medicine: Medical Sciences, Medicine Faculty, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Syamasundar, P. 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