孤独症患者药物以及药物靶点分析

Analysis of drugs and drug targets for patients with autism

目的通过分析孤独症患者外周血基因表达变化,推断可能用于孤独症治疗的药物和靶基因。方法以20对孤独症和正常对照患者的外周血RNA测序结果为研究对象,通过差异基因分析建立差异基因间的相互作用网络并筛选关键基因。在计算药物靶基因集的富集分数后,利用Logistic回归和Limma包两种方式筛选潜在应用价值的差异药物。在筛选到差异药物和差异靶基因的基础上,利用药物靶基因集建立药物和靶基因间的相互作用网络,推断可能用于孤独症治疗的药物和靶基因。结果利用Logistic和Limma两种方法共同筛选30种药物。通过差异基因分析,共筛选得到163个差异基因,这些基因与免疫功能、神经系统功能和机体代谢功能密切相关。FRK蛋白是多个孤独症药物的靶基因。视黄醇、4-oxoretinol、特布他林以及异氟烷可以作为候选药物。结论孤独症患者基因表达的变化与患者症状密切相关,本研究通过对转录组进行分析,筛出的药物和药物靶基因与孤独症密切相关,可以作为候选治疗靶点和药物。

Objective Inferring possible drugs and target genes for autism treatment by analyzing changes in peripheral blood gene expression in autism patients.Methods Peripheral blood RNA sequencing results from 20 pairs of autism and normal control patients were used to screen key genes by differential gene analysis and establishing interaction networks between differential genes.After calculating the enrichment scores of the drug target gene set,both Logistic regression and Limma package were used to screen the differential drugs with potential application value.Based on the screening of the differential enriched drugs and differential expressed target genes,the drug-target interaction gene set was used to establish the interaction network between drugs and target genes to infer the drugs and target genes that might be used for autism treatment.Results Both Logistic and Limma methods were used to screen 30 drugs together.The differential gene analysis resulted in 163 differential genes,which are closely related to immune function,neurological function and metabolic function of the organism.FRK protein is the target gene of several autism drugs.Retinol,4-oxoretinol,terbutaline,and isoflurane can be used as drug candidates.Conclusion Changes in gene expression in autism patients are closely related to patient symptoms.The drugs and drug targets screened by transcriptome analysis in this study,are closely related to autism,and may be used as candidate therapeutic targets and drugs.