Karimi Nafiseh, Motovali-Bashi Majid, Ghaderi-Zefrehei Mostafa
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Department of Animal Genetics, Yasouj University, Yasuj, Iran.
Front Neurol. 2023 Mar 9;14:1090631. doi: 10.3389/fneur.2023.1090631. eCollection 2023.
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.
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 show that the , and genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase ( < 0.05) in and gene expression levels in MS patients compared to that in controls. However, a significant down regulation of gene was observed in the same comparison.
This study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.
多发性硬化症(MS)是一种中枢神经系统的非传染性慢性疾病,是一种不可预测的间接遗传性疾病,以不同方式影响着不同的人。利用组学平台(基因组学、转录组学、蛋白质组学、表观基因组学、相互作用组学和代谢组学)数据库,现在有可能构建合理的系统生物学模型,以全面了解MS,并识别出揭示个性化治疗工具的途径。
在本研究中,我们使用了多个贝叶斯网络来寻找驱动MS疾病的转录基因调控网络。我们使用了一组使用R附加包bnlearn的BN算法。对BN结果进行了进一步的下游分析,并使用多种Cytoscape算法、基于网络的计算工具以及对56例MS患者和44例健康对照的血样进行qPCR扩增来进行验证。对结果进行语义整合,以增进对MS潜在复杂分子结构的理解,区分不同的代谢途径,并为发现相关基因和可能的新治疗方法提供有价值的基础。
结果表明, 、 和 基因最有可能在MS发展中发挥生物学作用。qPCR结果显示,与对照组相比,MS患者中 和 基因的表达水平显著升高( < 0.05)。然而,在相同比较中观察到 基因显著下调。
本研究为深入了解MS潜在的基因调控提供了潜在的诊断和治疗生物标志物。