他克莫司的生物信息学分析及其对自闭症谱系障碍的潜在治疗意义

目的：探讨他克莫司对自闭症谱系障碍的潜在治疗作用。方法：从基因表达谱数据库获取他克莫司及自闭症谱系障碍的数据，分别进行差异分析、基因本体学富集分析、京都基因与基因组百科全书富集分析、蛋白质相互作用网络分析并筛选关键基因，将二者的差异基因及KEGG通路进行关联分析，以及利用表观精准治疗预测平台进行药物与疾病关联分析，筛选出与他克莫司相关的疾病、药物及体内作用靶点，并在中文、英文数据库中检索自闭症谱系障碍与关键基因作用的相关文献加以验证。结果：他克莫司组共筛选出差异基因451个，其中基因本体学富集的基因大多参与小分子分解代谢过程、过氧化物酶体基质、黄素腺嘌呤二核苷酸结合、烟酰胺腺嘌呤二核苷酸磷酸结合等过程；京都基因与基因组百科全书通路富集主要和炎症反应、补体和凝血系统、氧化应激、过氧化物酶体增殖物激活受体信号通路、丝裂原活化蛋白激酶信号通路、哺乳动物雷帕霉素靶点信号通路等过程或功能相关。结合表观精准治疗预测平台的计算结果，发现他克莫司对全基因组表达谱的影响复杂，在蛋白质相互作用网络中共得到449个蛋白，筛选出12个关键基因，主要与细胞周期进程、炎症反应、免疫反应等功能相关；他克莫司和自闭症谱系障碍有关联。并验证了关键靶点的有效性。结论：他克莫司对免疫反应、炎症反应、细胞周期等过程或通路具有调控作用，其可能在抑制免疫反应的同时，还具有抑制神经炎症的功能，对自闭症谱系障碍患者有潜在的治疗意义。

Bioinformatics analysis of Tacrolimus and its potential therapeutic significance for Autism Spectrum Disorders

Objective The potential therapeutic effect of Tacrolimus on Autism Spectrum Disorders (ASD) was explored. Methods The data of Tacrolimus and ASD were obtained from Gene Expression Omnibus (GEO) to conduct differential analysis, Gene Ontology (go) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Protein-Protein Interaction (PPI) Network analysis, in which key genes were screened and the association analysis of their differential genes and KEGG pathway were made. Meanwhile, the Epigenomic Precision Medicine Prediction Platform (EpiMed) was used to analyze the association between drugs and diseases, so as to screen diseases, drugs and in vivo action targets related to Tacrolimus, and the literature on the role of ASD and key genes were searched in Chinese and English databases for verification. Results A total of 451 differential genes were screened, including 120 up-regulated and 331 down-regulated. Most of the genes enriched by GO are involved in small molecule catabolism, peroxisome matrix, flavin adenine dinucleotide binding, NADP binding and other processes. The enrichment of KEGG pathway is mainly related to processes or functions such as inflammatory reaction, complement and coagulation system, oxidative stress, PPAR signal pathway, MAPK signal pathway, mTOR signal pathway, etc. Combined with the calculation results of the EpiMed platform, it is found that tacrolimus has complex effects on the whole genome expression profile. In PPI, a total of 449 proteins were obtained, and 12 hub genes were selected, which are mainly related to cell cycle process, inflammatory response, immune response and other functions. Through text mining, a total of 46 literatures related to the role of ASD and key targets were retrieved to verify the effectiveness of key targets. Conclusion Tacrolimus has a regulatory effect on immune response, inflammatory response, cell cycle and other processes or pathways. It may inhibit neuroinflammation while inhibiting immune response, which has potential therapeutic significance for patients with ASD.