目的 探究智力障礙與雙硫死亡之間的聯(lián)系，為智力障礙的治療提供新的方向。方法 利用GEO數(shù)據(jù)庫中的智力障礙數(shù)據(jù)集（GSE64380），結(jié)合鐵死亡數(shù)據(jù)庫中的雙硫死亡相關(guān)基因確定與智力障礙相關(guān)的雙硫死亡基因，采用多因素Logistic分析、LASSO回歸模型和隨機(jī)森林模型（結(jié)合SHAP算法）進(jìn)行機(jī)器學(xué)習(xí)。在中藥入血成分?jǐn)?shù)據(jù)庫DCABM-TCM中以置信度得分0.90（LR＝124）為篩選標(biāo)準(zhǔn)，確定與雙硫死亡基因相關(guān)的中藥入血活性化合物。在TCMSP數(shù)據(jù)庫中檢索中藥活性化合物的類藥性（DL）、口服生物利用度（OB），進(jìn)行分子對接。結(jié)果 經(jīng)過多因素Logistic分析、LASSO回歸模型以及隨機(jī)森林模型（結(jié)合SHAP算法）的綜合分析，最終確定ACTC1是與智力障礙相關(guān)的雙硫死亡的關(guān)鍵基因。分子對接結(jié)果顯示，ACTC1與環(huán)拉酸、D-甘露糖苷、β-乳糖、D-吡喃葡萄糖、β-D-呋喃果糖有良好的結(jié)合性。根據(jù)中藥活性化合物的DL、OB值，確定D-吡喃葡萄糖和β-D-呋喃果糖是最具潛力的中藥活性化合物。扁豆全株被確定為潛在的研究中藥。結(jié)論 ACTC1被確認(rèn)為與智力障礙相關(guān)的雙硫死亡的關(guān)鍵基因，而扁豆中的活性化合物D-吡喃葡萄糖和β-D-呋喃果糖則被視為潛在的治療藥物。

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 and β-D-fructose furan. According to the values of DL and OB, D-glucopyranose and β-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 and β-D-fructofuranose in lentils are considered potential therapeutic agents.

R285.5