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创伤后应激障碍的非编码 RNA 研究数据整合与数据挖掘
其他题名Data integration and data mining for non-coding RNA studies of post-traumatic stress disorder
张萦倩
导师张昆林
2022-06
摘要创伤后应激障碍(post-traumatic stress disorder,PTSD)通常发生在个体经历或目睹创伤性事件之后,是一种具有复杂病因学的精神疾病。非编码 RNA(non-coding RNA, ncRNA)是从基因组上转录而来但不编码蛋白的 RNA,具有调控作用的 ncRNAs 可以调控基因表达, 参与生理病理过程,因而与人类疾病的发生发展密切相关。近年来,PTSD 的非编码 RNA 研究逐年增长,强调了 ncRNAs 在PTSD 发生发展中的重要作用;但由于不同研究中涉及的研究方法和人口学变量等的选择存在差异,导致研究间异质性较高,研究结果难以重复,阻碍了对 PTSD病理机制的进一步探索;另一方面,由于 ncRNAs 的种类和数量繁多,存在 ncRNA和靶基因多对多的关系,导致 PTSD 的非编码 RNA 研究报告的结果庞杂不一。 本研究旨在对已有的 PTSD 非编码 RNA 研究进行全面的检索和整合,在此基础上完成数据挖掘并进行可视化呈现。通过对关键词检索得到的 253 篇文献进行摘要阅读和筛选,最终获得了 37 篇 PTSD 相关的非编码 RNA 研究,再通过人工精读,提取出研究的研究设计信息,如样本的选择、PTSD 的测量与诊断、非编码 RNA 种类及其测量方法,以及标志物及其统计结果等,将这些内容汇总为PTSD 非编码 RNA 的核心数据。研究发现一些 ncRNAs 与 PTSD 的关联被反复验证,如 miR-19b、miR-193a-5p;还有一些高度保守的 miRNA 呈现出与 PTSD关联的跨物种一致性,如 let-7d-5p、miR-221、miR-132。接下来,利用已有的非编码 RNA 数据库,对研究中报告的 PTSD 关联 ncRNAs 进行基本信息检索,并分物种(人类、大鼠和小鼠)获取 ncRNAs 的靶基因集;基于 R 语言开发的ClusterProfiler 包,本研究对 ncRNAs 的靶基因集进行了 KEGG 和 GO 通路富集分析,发现 PTSD 的 ncRNAs 主要参与细胞生长发育、压力应激反应、免疫炎症及神经系统等相关通路的调控。接着,本研究从 RNA 调控层面出发,探索 PTSD与相关精神疾病(精神分裂症、重度抑郁症和物质滥用障碍)间重叠的生物机制;结果显示,PTSD 与这些相关精神疾病间共有的调控机制是与激素调控和信号传导相关的通路。通过更新 MySQL 关系型数据库的 E-R 关系及内容,本研究最终将会把 PTSD 非编码 RNA 的核心数据呈现到课题组的数据库 PTSDepigenetics 网站(http://ptsdepigenetics.psych.ac.cn/)中,为研究者提供快捷便利的检索功能和相关领域的前沿进展。 本研究对已有的 PTSD 非编码 RNA 研究进行了详细的梳理和整合,并通过对 PTSD 关联的 ncRNAs 进行数据挖掘分析,对 PTSD 的生理病理机制提供了一定的见解,希望能为相关领域的研究者提供启发和便利。
其他摘要Post-traumatic stress disorder (PTSD) is a mental disorder with complex etiology, which usually occurs after individuals experience or witness traumatic events. Non- coding RNAs (ncRNAs) are RNAs transcribed from the genome, which do not encode proteins. Regulatory ncRNAs can regulate gene expression and participate in physiological and pathological processes, they are closely related to the occurrence and development of human diseases. Studies of ncRNAs of PTSD has increased year by year, emphasizing the important role of ncRNAs in the pathogenesis of PTSD. However, the huge varieties and numbers of ncRNAs and their many-to-many relationship with target genes result in the different association between ncRNAs and PTSD. On the other hand, due to differences of research methods and demographic variables, the heterogeneity among different studies cannot be ignored, and the significant results are difficult to be replicated, which hinders further exploration of the pathological mechanism of PTSD. This study aims to comprehensively retrieve and integrate studies reported associations between ncRNAs and PTSD, and on this basis, further investigate the role of ncRNAs in regulating PTSD development. 253 articles were screened by reading abstract, 37 ncRNAs researches of PTSD were included in this study eventually. Then, through reading the full articles and manually extracting the study information, such as selection of samples, measurement and diagnosis of PTSD, types of ncRNAs and relevant measuring methods, as well as specific markers and their statistical results, the core data of PTSD-ncRNAs were constructed. The association between some ncRNAs and PTSD has been repeatedly verified, such as miR-19b and miR-193a-5p. Besides, some highly conserved miRNAs showed cross-species consistent association with PTSD, such as let-7d-5p, miR-221, and miR-132. Next, using non-coding RNA databases to retrieve the basic information of the ncRNAs associated with PTSD, and obtain the target gene sets of ncRNAs by species (human, rat, and mouse). Based on ClusterProfiler, package developed by R language, the KEGG and GO enrichment pathway were analyzed for the target gene set of ncRNAs, and results demonstrates that the PTSD ncRNAs are significantly involved in the regulation of cell growth and development, stress response, immune inflammation, and nervous system related pathways. Furthermore, this study explored the overlap biological mechanisms between PTSD and related psychiatric disorders (schizophrenia, major depression, and substance abuse disorder) from the aspect of RNA regulation. Results suggests that the common regulatory mechanisms between PTSD and these related psychiatric disorders are pathways related to hormone regulation and signal transduction. By updating the E- R relation and content of MySQL relational database, the core data of PTSD-ncRNAs information will be presented on the PTSDepigenetics (http://ptsdepigenetics.psych.ac.cn/), providing researchers with quick and convenient retrieval function and related fields of cutting-edge progress. In this study, the existing ncRNAs studies for PTSD were reviewed and integrated in details, and some insights on the pathogenesis of PTSD were proposed through data mining analysis of ncRNAs associated with PTSD, hoping to provide inspiration and convenience for researchers in related fields.
关键词创伤后应激障碍 非编码 RNA 生物信息学 数据挖掘
学位类型硕士
语种中文
学位名称理学硕士
学位专业应用心理
学位授予单位中国科学院大学
学位授予地点中国科学院心理研究所
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/43208
专题健康与遗传心理学研究室
推荐引用方式
GB/T 7714
张萦倩. 创伤后应激障碍的非编码 RNA 研究数据整合与数据挖掘[D]. 中国科学院心理研究所. 中国科学院大学,2022.
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