Gene network reveals LASP1, TUBA1C, and S100A6 are likely playing regulatory roles in multiple sclerosis

Nafiseh Karimi; Majid Motovali-Bashi; Mostafa Ghaderi-Zefrehei

doi:10.3389/fneur.2023.1090631

Gene network reveals LASP1, TUBA1C, and S100A6 are likely playing regulatory roles in multiple sclerosis

Front Neurol. 2023 Mar 9:14:1090631. doi: 10.3389/fneur.2023.1090631. eCollection 2023.

Authors

Nafiseh Karimi¹, Majid Motovali-Bashi¹, Mostafa Ghaderi-Zefrehei²

Affiliations

¹ Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
² Department of Animal Genetics, Yasouj University, Yasuj, Iran.

Abstract

Introduction: Multiple sclerosis (MS), a non-contagious and chronic disease of the central nervous system, is an unpredictable and indirectly inherited disease affecting different people in different ways. Using Omics platforms genomics, transcriptomics, proteomics, epigenomics, interactomics, and metabolomics database, it is now possible to construct sound systems biology models to extract full knowledge of the MS and recognize the pathway to uncover the personalized therapeutic tools.

Methods: In this study, we used several Bayesian Networks in order to find the transcriptional gene regulation networks that drive MS disease. We used a set of BN algorithms using the R add-on package bnlearn. The BN results underwent further downstream analysis and were validated using a wide range of Cytoscape algorithms, web based computational tools and qPCR amplification of blood samples from 56 MS patients and 44 healthy controls. The results were semantically integrated to improve understanding of the complex molecular architecture underlying MS, distinguishing distinct metabolic pathways and providing a valuable foundation for the discovery of involved genes and possibly new treatments.

Results: Results show that the LASP1, TUBA1C, and S100A6 genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase (P < 0.05) in LASP1 and S100A6 gene expression levels in MS patients compared to that in controls. However, a significant down regulation of TUBA1C gene was observed in the same comparison.

Conclusion: This study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.

Keywords: Bayesian network; Cytoscape; multiple sclerosis (MS); qPCR; transcriptome.

Grants and funding

This study was funded with the budget of the University of Isfahan (use of laboratory equipment and purchase of materials) and the Biotechnology Development Headquarters (grant for purchase of laboratory materials).