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采用多组学方法、机器学习和对接技术探索阿尔茨海默病的潜在治疗靶点。

Exploring Plausible Therapeutic Targets for Alzheimer's Disease using Multi-omics Approach, Machine Learning and Docking.

机构信息

Department of Biotechnology, Bhupat and Jyoti Mehta School of BioSciences, Indian Institute of Technology Madras, Chennai, 600 036, Tamilnadu, India.

Department of Pharmaceutical Engineering, Vinayaka Mission\'s Kirupananda Variyar Engineering College, Salem, India.

出版信息

Curr Top Med Chem. 2022;22(22):1868-1879. doi: 10.2174/1568026622666220902110115.

Abstract

The progressive deterioration of neurons leads to Alzheimer's disease (AD), and developing a drug for this disorder is challenging. Substantial gene/transcriptome variability from multiple cell types leads to downstream pathophysiologic consequences that represent the heterogeneity of this disease. Identifying potential biomarkers for promising therapeutics is strenuous due to the fact that the transcriptome, epigenetic, or proteome changes detected in patients are not clear whether they are the cause or consequence of the disease, which eventually makes the drug discovery efforts intricate. The advancement in scRNA-sequencing technologies helps to identify cell type-specific biomarkers that may guide the selection of the pathways and related targets specific to different stages of the disease progression. This review is focussed on the analysis of multi-omics data from various perspectives (genomic and transcriptomic variants, and single-cell expression), which provide insights to identify plausible molecular targets to combat this complex disease. Further, we briefly outlined the developments in machine learning techniques to prioritize the risk-associated genes, predict probable mutations and identify promising drug candidates from natural products.

摘要

神经元的进行性恶化导致阿尔茨海默病(AD),开发针对这种疾病的药物具有挑战性。来自多种细胞类型的大量基因/转录组变异导致下游病理生理后果,代表了这种疾病的异质性。由于在患者中检测到的转录组、表观遗传或蛋白质组变化不清楚它们是疾病的原因还是结果,因此确定有前途的治疗方法的潜在生物标志物非常困难,这最终使得药物发现工作变得复杂。单细胞 RNA 测序技术的进步有助于识别细胞类型特异性生物标志物,这些标志物可能有助于选择与疾病进展不同阶段相关的途径和相关靶点。本综述重点从多个角度(基因组和转录组变异以及单细胞表达)分析多组学数据,为识别合理的分子靶点以对抗这种复杂疾病提供了思路。此外,我们简要概述了机器学习技术的发展,以优先考虑风险相关基因,预测可能的突变,并从天然产物中识别有前途的药物候选物。

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