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Transcriptomic profiles in Parkinson’s disease
Experimental Biology and Medicine ( IF 2.8 ) Pub Date : 2020-11-04 , DOI: 10.1177/1535370220967325
Lille Kurvits 1, 2 , Freddy Lättekivi 3 , Ene Reimann 4 , Liis Kadastik-Eerme 1, 5 , Kristjan M Kasterpalu 6 , Sulev Kõks 7, 8 , Pille Taba 1, 5 , Anu Planken 1, 5, 9
Affiliation  

Transcriptomics in Parkinson’s disease offers insights into the pathogenesis of Parkinson’s disease but obtaining brain tissue has limitations. In order to bypass this issue, we profile and compare differentially expressed genes and enriched pathways (KEGG) in two peripheral tissues (blood and skin) of 12 Parkinson’s disease patients and 12 healthy controls using RNA-sequencing technique and validation with RT-qPCR. Furthermore, we compare our results to previous Parkinson’s disease post mortem brain tissue and blood results using the robust rank aggregation method. The results show no overlapping differentially expressed genes or enriched pathways in blood vs. skin in our sample sets (25 vs. 1068 differentially expressed genes with an FDR ≤ 0.05; 1 vs. 9 pathways in blood and skin, respectively). A meta-analysis from previous transcriptomic sample sets using either microarrays or RNA-Seq yields a robust rank aggregation list of cortical gene expression changes with 43 differentially expressed genes; a list of substantia nigra changes with 2 differentially expressed genes and a list of blood changes with 1 differentially expressed gene being statistically significant at FDR ≤ 0.05. In cortex 1, KEGG pathway was enriched, four in substantia nigra and two in blood. None of the differentially expressed genes or pathways overlap between these tissues. When comparing our previously published skin transcription analysis, two differentially expressed genes between the cortex robust rank aggregation and skin overlap. In this study, for the first time a meta-analysis is applied on transcriptomic sample sets in Parkinson’s disease. Simultaneously, it explores the notion that Parkinson’s disease is not just a neuronal tissue disease by exploring peripheral tissues. The comparison of different Parkinson’s disease tissues yields surprisingly few significant differentially expressed genes and pathways, suggesting that divergent gene expression profiles in distinct cell lineages, metabolic and possibly iatrogenic effects create too much transcriptomic noise for detecting significant signal. On the other hand, there are signs that point towards Parkinson’s disease-specific changes in non-neuronal peripheral tissues in Parkinson’s disease, indicating that Parkinson’s disease might be a multisystem disorder.



中文翻译:


帕金森病的转录组学特征



帕金森病的转录组学可以深入了解帕金森病的发病机制,但获取脑组织有其局限性。为了绕过这个问题,我们使用 RNA 测序技术和 RT-qPCR 验证,对 12 名帕金森病患者和 12 名健康对照的两个外周组织(血液和皮肤)中的差异表达基因和富集通路 (KEGG) 进行了分析和比较。此外,我们使用稳健的排名聚合方法将我们的结果与之前的帕金森病死后脑组织和血液结果进行比较。结果显示,在我们的样本集中,血液与皮肤中没有重叠的差异表达基因或富集通路(FDR ≤ 0.05 的差异表达基因分别为 25 条和 1068 条;血液和皮肤中分别为 1 条和 9 条通路)。使用微阵列或 RNA-Seq 对先前的转录组样本集进行荟萃分析,产生了包含 43 个差异表达基因的皮质基因表达变化的强大排名聚合列表;具有 2 个差异表达基因的黑质变化列表和具有 1 个差异表达基因的血液变化列表,在 FDR ≤ 0.05 时具有统计显着性。在皮质 1 中,KEGG 通路富集,其中 4 个在黑质中,2 个在血液中。这些组织之间没有差异表达的基因或途径重叠。当比较我们之前发表的皮肤转录分析时,皮层稳健等级聚合和皮肤重叠之间的两个差异表达基因。在这项研究中,首次对帕金森病的转录组样本集进行荟萃分析。 同时,它通过探索外周组织,探讨了帕金森病不仅仅是一种神经组织疾病的概念。不同帕金森病组织的比较令人惊讶地发现很少有显着差异表达的基因和通路,这表明不同细胞谱系、代谢和可能的医源性效应中不同的基因表达谱会产生过多的转录组噪声,无法检测显着的信号。另一方面,有迹象表明帕金森病的非神经元周围组织出现了帕金森病特异性的变化,表明帕金森病可能是一种多系统疾病。

更新日期:2020-11-06
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