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一种综合方法来揭示阿尔茨海默病和帕金森病中假定的串扰网络。

An integrated approach to unravel a putative crosstalk network in Alzheimer's disease and Parkinson's disease.

机构信息

Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi, 110042, India.

Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi, 110042, India.

出版信息

Neuropeptides. 2020 Oct;83:102078. doi: 10.1016/j.npep.2020.102078. Epub 2020 Aug 12.

Abstract

Integration of multiple profiling data and construction of functional regulatory networks provide a powerful approach to uncover functional relationships and significant molecular entities from transcriptomic data, highlighting the molecular mechanisms of complex diseases. Despite having an overlap in the neuropathologies of AD and PD, the molecular entities overlapped and mechanisms behind them are less known. Here we used an integrated strategy to analyze miRNA and gene transcriptomic data to understand the role of miRNAs and genes in regulatory activities taking place in cells, and find transcriptomic signatures linking AD and PD. We preprocessed and analyzed publicly available microarray datasets and identified 97 DEGs and 21 DEmiRs that may be involved in the overlapped mechanisms between these two disorders. Among the DEGs, we found HSPA9, PGK1, SDHC, FH, DLD, YWHAZ and ACLY as the major protein-coding genes involved in the crosstalk for AD-PD pathogenesis. Further we integrated these DEGs and DEmiRs with regulatory TFs to construct an overlapped dysregulated network of AD and PD. In the network, miR-27a-3p, miR-148a-3p and miR-15a-5p were found to be the most relevant with maximum interactions, describing their significance in the potential crosstalk. We also looked into the dysregulated biological processes and pathways overlapped in AD and PD. In conclusion, we highlighted the DEGs, DEmiRs, their interactions and related pathways overlapped in AD and PD pathogenesis, also describing a potential crosstalk at molecular level. Besides, our findings can further be used for molecular studies to reveal an assured AD-PD crosstalk.

摘要

整合多种分析数据并构建功能调控网络,为从转录组数据中揭示功能关系和重要分子实体提供了强大的方法,突出了复杂疾病的分子机制。尽管 AD 和 PD 的神经病理学有重叠,但重叠的分子实体及其背后的机制知之甚少。在这里,我们使用综合策略来分析 miRNA 和基因转录组数据,以了解 miRNA 和基因在细胞中发生的调控活动中的作用,并找到将 AD 和 PD 联系起来的转录组特征。我们预处理和分析了公开的微阵列数据集,并确定了 97 个差异表达基因(DEGs)和 21 个差异表达 miRNA(DEmiRs),它们可能参与了这两种疾病的重叠机制。在 DEGs 中,我们发现 HSP9、PGK1、SDHC、FH、DLD、YWHAZ 和 ACLY 是 AD-PD 发病机制中主要涉及串扰的蛋白质编码基因。进一步将这些 DEGs 和 DEmiRs 与调控转录因子整合,构建 AD 和 PD 的重叠失调网络。在该网络中,miR-27a-3p、miR-148a-3p 和 miR-15a-5p 被发现与最大相互作用的相关度最高,描述了它们在潜在串扰中的重要性。我们还研究了 AD 和 PD 中重叠失调的生物过程和途径。总之,我们强调了 AD 和 PD 发病机制中差异表达基因、差异表达 miRNA、它们的相互作用和相关途径的重叠,并描述了分子水平上的潜在串扰。此外,我们的发现还可以进一步用于分子研究,以揭示可靠的 AD-PD 串扰。

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