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通过生物信息学方法识别帕金森病和双相情感障碍共有的重要生物标志物及药物靶点:一项初步研究

Bioinformatics Approach to Identify Significant Biomarkers, Drug Targets Shared Between Parkinson's Disease and Bipolar Disorder: A Pilot Study.

作者信息

Hossain Md Bipul, Islam Md Kobirul, Adhikary Apurba, Rahaman Abidur, Islam Md Zahidul

机构信息

Department of Information and Communication Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh.

Department of Information and Communication Technology, Islamic University, Kushtia, Bangladesh.

出版信息

Bioinform Biol Insights. 2022 Feb 23;16:11779322221079232. doi: 10.1177/11779322221079232. eCollection 2022.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder responsible for shaking, rigidity, and trouble in walking and patients' coordination ability and physical stability deteriorate day by day. Bipolar disorder (BD) is a psychiatric disorder which is the reason behind extreme shiftiness in mood, and frequent mood inversion may reach too high called mania. People with BD have a greater chance of developing PD during the follow-up period. A lot of work has been done to understand the key factors for developing these 2 diseases. But the molecular functionalities that trigger the development of PD in people with BD are not clear yet. In our study, we are intended to identify the molecular biomarkers and pathways shared between BD and PD. We have investigated the RNA-Seq gene expression data sets of PD and BD. A total of 45 common unique genes (32 up-regulated and 13 down-regulated) abnormally expressed in both PD and BD were identified by applying statistical methods on the GEO data sets. Gene ontology (GO) and BioCarta, KEGG, and Reactome pathways analysis of these 45 common dysregulated genes identified numerous altered molecular pathways such as mineral absorption, Epstein-Barr virus infection, HTLV-I infection, antigen processing, and presentation. Analysis of protein-protein interactions revealed 9 significant hub-proteins, namely RPL21, RPL34, CKS2, B2M, TNFRSF10A, DTX2, HLA-B, ATP2A3, and TAPBP. Significant transcription factors (IRF8, SPI1, RUNX1, and FOXA1) and posttranscriptional regulator microRNAs (hsa-miR-491-3p and hsa-miR-1246) are also found by analyzing gene-transcription factors and gene-miRNAs interactions, respectively. Protein-drug interaction analysis revealed hub-protein B2M's interaction with molecular drug candidates like -formylmethionine, 3-indolebutyric acid, and doxycycline. Finally, a link between pathological processes of PD and BD is identified at transcriptional level. This study may help us to predict the development of PD among the people suffering from BD and gives some clue to understand significant pathological mechanisms.

摘要

帕金森病(PD)是一种神经退行性疾病,会导致震颤、僵硬、行走困难,患者的协调能力和身体稳定性会日益恶化。双相情感障碍(BD)是一种精神疾病,是情绪极度多变的原因,频繁的情绪反转可能会达到称为躁狂的过高程度。双相情感障碍患者在随访期间患帕金森病的几率更高。为了了解引发这两种疾病的关键因素,已经开展了大量工作。但是,触发双相情感障碍患者患帕金森病的分子功能尚不清楚。在我们的研究中,我们旨在确定双相情感障碍和帕金森病之间共有的分子生物标志物和途径。我们研究了帕金森病和双相情感障碍的RNA测序基因表达数据集。通过对GEO数据集应用统计方法,共鉴定出45个在帕金森病和双相情感障碍中均异常表达的共同独特基因(32个上调和13个下调)。对这45个共同失调基因进行基因本体论(GO)以及BioCarta、KEGG和Reactome途径分析,确定了许多改变的分子途径,如矿物质吸收、爱泼斯坦-巴尔病毒感染、人类嗜T淋巴细胞病毒I型感染、抗原加工和呈递。蛋白质-蛋白质相互作用分析揭示了9种重要的枢纽蛋白,即核糖体蛋白L21、核糖体蛋白L34、细胞周期蛋白依赖性激酶2、β2微球蛋白、肿瘤坏死因子受体超家族成员10A、泛素蛋白连接酶2、人类白细胞抗原B、肌浆网/内质网钙ATP酶3和TAP结合蛋白。通过分别分析基因-转录因子和基因-微小RNA相互作用,还发现了重要的转录因子(干扰素调节因子8、SPI1、RUNX1和叉头框蛋白A1)和转录后调节微小RNA(hsa-miR-491-3p和hsa-miR-1246)。蛋白质-药物相互作用分析揭示了枢纽蛋白β2微球蛋白与甲酰甲硫氨酸、3-吲哚丁酸和强力霉素等分子候选药物的相互作用。最后,在转录水平上确定了帕金森病和双相情感障碍病理过程之间的联系。这项研究可能有助于我们预测双相情感障碍患者中帕金森病的发展,并为理解重要的病理机制提供一些线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bc3/8874170/54f49b30a597/10.1177_11779322221079232-fig1.jpg

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