A Systems Biology Approach to Identifying Genetic Markers that Link Progression of Parkinson’s Disease to Risk Factors related to Ageing, Lifestyle and Type 2 Diabetes

Najmus Sakib, Utpala Nanda Chowdhury, M. Islam, F. Huq, Julian M. W. Quinn, M. Moni
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引用次数: 3

Abstract

The processes that underlie Parkinsons disease (PD) are still unclear, but improved comprehension of genetic and environmental influences on PD, and how these influences interact will help find new approaches to reducing PD progression. We thus employed quantitative framework analysis to reveal some of the complex relationship of various genetic factors affecting PD. In this study, we analyzed gene expression microarray data from cells and tissues affected by PD, ageing (AG), type II diabetes (T2D), high body fat (HBF) and control datasets. We determined genetic associations of PD and these risk factors based on neighborhood-based benchmarking and multilayer network topology. We first identified 1343 significantly dysregulated genes in the PD patient tissues compared to healthy control, including we have 779 genes with down regulated expression and 544 genes up regulated. 45 genes were highly expressed in both for the PD and ageing; the number of shared genes for the PD and the type II diabetes is 51. Ontological and pathway analyses then identified significant gene ontology and molecular pathways that enhance our understanding of the fundamental molecular procedure of the PD progression. Therapeutic targets of the PD could be developed using these identified target genes, ontologies and pathways.
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系统生物学方法鉴定帕金森病进展与衰老、生活方式和2型糖尿病相关危险因素的遗传标记
帕金森病(PD)的发病机制尚不清楚,但对遗传和环境对PD的影响以及这些影响如何相互作用的理解的提高将有助于找到减少PD进展的新方法。因此,我们采用定量框架分析来揭示影响帕金森病的各种遗传因素之间的一些复杂关系。在这项研究中,我们分析了来自PD、衰老(AG)、II型糖尿病(T2D)、高体脂(HBF)和对照数据集的细胞和组织的基因表达微阵列数据。我们基于邻域基准和多层网络拓扑确定PD与这些危险因素的遗传关联。与健康对照相比,我们首先在PD患者组织中发现了1343个显著失调的基因,其中779个基因表达下调,544个基因表达上调。PD和衰老均高表达的基因有45个;PD和II型糖尿病共有51个基因。本体论和途径分析确定了重要的基因本体论和分子途径,增强了我们对帕金森病进展的基本分子过程的理解。利用这些已确定的靶基因、本体论和途径,可以开发PD的治疗靶点。
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