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Article

Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration

1
Department of Orthopaedics, Emory University, Atlanta, GA 30322, USA
2
Atlanta VA Medical Center, Decatur, GA 30033, USA
*
Author to whom correspondence should be addressed.
Genes 2020, 11(7), 771; https://doi.org/10.3390/genes11070771
Received: 15 June 2020 / Revised: 29 June 2020 / Accepted: 7 July 2020 / Published: 9 July 2020
(This article belongs to the Section Human Genomics and Genetic Diseases)
Intervertebral disc (IVD) degeneration (IDD) is a multifactorial physiological process which is often associated with lower back pain. Previous studies have identified some molecular markers associated with disc degeneration, which despite their significant contributions, have provided limited insight into the etiology of IDD. In this study, we utilized a network medicine approach to uncover potential molecular mediators of IDD. Our systematic analyses of IDD associated with 284 genes included functional annotation clustering, interaction networks, network cluster analysis and Transcription factors (TFs)-target gene network analysis. The functional enrichment and protein–protein interaction network analysis highlighted the role of inflammatory genes and cytokine/chemokine signaling in IDD. Moreover, sub-network analysis identified significant clusters possessing organized networks of 24 cytokine and chemokine genes, which may be considered as key modulators for IDD. The expression of these genes was validated in independent microarray datasets. In addition, the regulatory network analysis identified the role of multiple transcription factors, with RUNX1 being a master regulator in the pathogenesis of IDD. Our analyses highlighted the role of cytokine genes and interacting pathways in IDD and further improved our understanding of the genetic mechanisms underlying IDD. View Full-Text
Keywords: interaction network; pathway enrichment; regulatory-network; gene-ontology; transcription factor; network cluster; RUNX1 interaction network; pathway enrichment; regulatory-network; gene-ontology; transcription factor; network cluster; RUNX1
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MDPI and ACS Style

Khan, N.M.; Diaz-Hernandez, M.E.; Presciutti, S.M.; Drissi, H. Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration. Genes 2020, 11, 771. https://doi.org/10.3390/genes11070771

AMA Style

Khan NM, Diaz-Hernandez ME, Presciutti SM, Drissi H. Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration. Genes. 2020; 11(7):771. https://doi.org/10.3390/genes11070771

Chicago/Turabian Style

Khan, Nazir M., Martha E. Diaz-Hernandez, Steven M. Presciutti, and Hicham Drissi. 2020. "Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration" Genes 11, no. 7: 771. https://doi.org/10.3390/genes11070771

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