智力障碍与双硫死亡相关机制以及潜在靶向中药的预测  

Mechanism of intellectual disability and disulfide death and the prediction of potential targeted Chinese medicine

作　　者：罗正芳 王宁霞 LUO Zhengfang;WANG Ningxia(Department of Pediatric Rehabilitation,Yinchuan First People’s Hospital,Yinchuan 750001,China)

机构地区：[1]银川市第一人民医院儿童康复科,宁夏银川750001

出　　处：《现代药物与临床》2024年第7期1681-1688,共8页Drugs & Clinic

摘　　要：目的 探究智力障碍与双硫死亡之间的联系,为智力障碍的治疗提供新的方向。方法 利用GEO数据库中的智力障碍数据集(GSE64380),结合铁死亡数据库中的双硫死亡相关基因确定与智力障碍相关的双硫死亡基因,采用多因素Logistic分析、LASSO回归模型和随机森林模型(结合SHAP算法)进行机器学习。在中药入血成分数据库DCABM-TCM中以置信度得分0.90(LR=124)为筛选标准,确定与双硫死亡基因相关的中药入血活性化合物。在TCMSP数据库中检索中药活性化合物的类药性(DL)、口服生物利用度(OB),进行分子对接。结果 经过多因素Logistic分析、LASSO回归模型以及随机森林模型(结合SHAP算法)的综合分析,最终确定ACTC1是与智力障碍相关的双硫死亡的关键基因。分子对接结果显示,ACTC1与环拉酸、D-甘露糖苷、β-乳糖、D-吡喃葡萄糖、β-D-呋喃果糖有良好的结合性。根据中药活性化合物的DL、OB值,确定D-吡喃葡萄糖和β-D-呋喃果糖是最具潜力的中药活性化合物。扁豆全株被确定为潜在的研究中药。结论 ACTC1被确认为与智力障碍相关的双硫死亡的关键基因,而扁豆中的活性化合物D-吡喃葡萄糖和β-D-呋喃果糖则被视为潜在的治疗药物。Objective To explore the relationship between intellectual disability and disulfide death,and provide a new direction for the treatment of intellectual disability.Method The disulfide death genes associated with intellectual disability were identified by the data set of intellectual disability in GEO database(GSE64380)and combined with disulfide death genes in iron death database.Multi-factor Logistic analysis,LASSO regression model and random forest model(combined with SHAP algorithm)were used for machine learning.In DCABM-TCM database,confidence score 0.90(LR=124)was used as the screening criterion to identify the active compounds related to disulfide death genes.The medicinal properties(DL)and oral bioavailability(OB)of the active compounds were searched in TCMSP database for molecular docking.Result After multivariate Logistic analysis,LASSO regression model and random forest model(combined with SHAP algorithm)comprehensive analysis,ACTC1 was finally determined to be the key gene of disulfide death related to intellectual disability.The results of molecular docking showed that ACTC1 had good binding with cyclonic acid,D-mannoside,β-lactose,D-glucopyranose andβ-D-fructose furan.According to the values of DL and OB,D-glucopyranose andβ-D-fructofuran were identified as the most potential active compounds in Chinese medicine.Whole lentil plants were identified as potential Chinese medicinal materials for study.Conclusion ACTC1 has been identified as a key gene associated with intellectual disabilities and disulfide death,while the active compounds D-pyranose glucose andβ-D-fructofuranose in lentils are considered potential therapeutic agents.

关 键 词：智力障碍 双硫死亡 机器学习 分子对接 扁豆 D-吡喃葡萄糖 β-D-呋喃果糖 

分 类 号：R285.5[医药卫生—中药学]