Bioinformatics Prediction for Network-Based Integrative Multi-Omics Expression Data Analysis in Hirschsprung Disease

Hirschsprung's disease (HSCR) is a rare developmental disorder in which enteric ganglia are missing along a portion of the intestine. HSCR has a complex inheritance, with as the major disease-causing gene. However, the pathogenesis of HSCR is still not completely understood. Therefore, we appli...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2024-01, Vol.14 (2), p.164
Main Authors: Lucena-Padros, Helena, Bravo-Gil, Nereida, Tous, Cristina, Rojano, Elena, Seoane-Zonjic, Pedro, Fernández, Raquel María, Ranea, Juan A G, Antiñolo, Guillermo, Borrego, Salud
Format: Article
Language:English
Subjects:
Analysis
Bioinformatics
Biomarkers
Causes and theories of causation
Colon
Computational Biology
Disease
Diseases
enteric neuropathy
Ganglia
Genes
Genetic aspects
Hirschsprung Disease - genetics
Hirschsprung's disease
Humans
MicroRNAs
MicroRNAs - genetics
miRNA
Multiomics
networks analysis
omics expression data
Online data bases
Physiological aspects
Proteins
system biology
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Summary:Hirschsprung's disease (HSCR) is a rare developmental disorder in which enteric ganglia are missing along a portion of the intestine. HSCR has a complex inheritance, with 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-protein interaction (PPI) and miRNA-target 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-disease 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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom14020164