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a rare developmental disorder in which enteric ganglia are missing along a portion of the intestine. HSCR has a complex inheritance, with RET as the major disease-causing gene. However, the pathogenesis of HSCR is still not completely understood. Therefore, we applied a computational approach based on multi-omics network characterization and clustering analysis for HSCR-related gene\/miRNA identification and biomarker discovery. Protein\u2013protein interaction (PPI) and miRNA\u2013target interaction (MTI) networks were analyzed by DPClusO and BiClusO, respectively, and finally, the biomarker potential of miRNAs was computationally screened by miRNA-BD. In this study, a total of 55 significant gene\u2013disease modules were identified, allowing us to propose 178 new HSCR candidate genes and two biological pathways. Moreover, we identified 12 key miRNAs with biomarker potential among 137 predicted HSCR-associated miRNAs. Functional analysis of new candidates showed that enrichment terms related to gene ontology (GO) and pathways were associated with HSCR. In conclusion, this approach has allowed us to decipher new clues of the etiopathogenesis of HSCR, although molecular experiments are further needed for clinical validations.<\/jats:p>","DOI":"10.3390\/biom14020164","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T07:49:47Z","timestamp":1706600987000},"page":"164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bioinformatics Prediction for Network-Based Integrative Multi-Omics Expression Data Analysis in Hirschsprung Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Helena","family":"Lucena-Padros","sequence":"first","affiliation":[{"name":"Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville, University Hospital Virgen del Roc\u00edo\/CSIC\/University of Seville, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nereida","family":"Bravo-Gil","sequence":"additional","affiliation":[{"name":"Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville, University Hospital Virgen del Roc\u00edo\/CSIC\/University of Seville, 41013 Seville, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tous","sequence":"additional","affiliation":[{"name":"Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville, University Hospital Virgen del Roc\u00edo\/CSIC\/University of Seville, 41013 Seville, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-710X","authenticated-orcid":false,"given":"Elena","family":"Rojano","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of Malaga, 29010 Malaga, Spain"},{"name":"Biomedical Research Institute of Malaga, IBIMA, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-1415","authenticated-orcid":false,"given":"Pedro","family":"Seoane-Zonjic","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of Malaga, 29010 Malaga, Spain"},{"name":"Biomedical Research Institute of Malaga, IBIMA, 29010 Malaga, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), 29071 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Mar\u00eda","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville, University Hospital Virgen del Roc\u00edo\/CSIC\/University of Seville, 41013 Seville, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A. 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