Identification and Characterization of Biomarkers and Their Role in Opioid Addiction by Integrated Bioinformatics Analysis.

Identification and Characterization of Biomarkers and Their Role in Opioid Addiction by Integrated Bioinformatics Analysis.
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通过综合生物信息学分析识别和表征生物标志物及其在阿片类药物成瘾中的作用

DOI:
10.3389/fnins.2020.608349
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发表时间:
2020
影响因子:
4.3
通讯作者:
Ma C
Ma C
中科院分区:
医学2区
文献类型:
--
作者:
Zhang X;Yu H;Bai R;Ma C

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虽然许多研究已经证实,阿片类药物成瘾的机制包括遗传和表观遗传方面,这些研究的结果是不一致的。在这里,我们从Gene Expression Omnibus数据库下载了基因表达谱信息GSE 87823。从年龄在19岁和35岁之间的男性中选择样本用于差异表达基因(DEG)的分析。使用京都基因和基因组百科全书(KEGG)途径和基因本体(GO)富集分析来分析与DEG相关的途径。我们进一步使用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并使用10种不同的计算方法来验证枢纽基因。最后,我们利用基本局部比对搜索工具(BLAST)来鉴定小鼠中具有最高序列相似性的DEG,并使用RT-qPCR检测该动物模型中枢纽基因的表达变化。我们确定了三个关键基因,ADCY 9,PECAM 1和IL 4。与对照小鼠相比,阿片类药物成瘾小鼠的丘脑核中ADCY 9表达减少,这与在人类中观察到的变化一致。本研究的重要性和创新性体现在两个方面。首先,我们使用了多种计算方法来获得枢纽基因;其次,我们利用同源性分析来解决无法在患者或健康个体中进行成瘾相关实验的难题。总之,本研究不仅探索了阿片类药物成瘾的潜在生物标志物和治疗靶点,而且为阿片类药物成瘾的后续研究提供了新的思路。
Although numerous studies have confirmed that the mechanisms of opiate addiction include genetic and epigenetic aspects, the results of such studies are inconsistent. Here, we downloaded gene expression profiling information, GSE87823, from the Gene Expression Omnibus database. Samples from males between ages 19 and 35 were selected for analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were used to analyze the pathways associated with the DEGs. We further constructed protein-protein interaction (PPI) networks using the STRING database and used 10 different calculation methods to validate the hub genes. Finally, we utilized the Basic Local Alignment Search Tool (BLAST) to identify the DEG with the highest sequence similarity in mouse and detected the change in expression of the hub genes in this animal model using RT-qPCR. We identified three key genes, ADCY9, PECAM1, and IL4. ADCY9 expression decreased in the nucleus accumbens of opioid-addicted mice compared with control mice, which was consistent with the change seen in humans. The importance and originality of this study are provided by two aspects. Firstly, we used a variety of calculation methods to obtain hub genes; secondly, we exploited homology analysis to solve the difficult challenge that addiction-related experiments cannot be carried out in patients or healthy individuals. In short, this study not only explores potential biomarkers and therapeutic targets of opioid addiction but also provides new ideas for subsequent research on opioid addiction.
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