Genes · 2025
Integrating Transcriptomics, Network Pharmacology, and Machine Learning to Reveal Transglutaminase 2 (TGM2) as a Key Target Mediating Taurocholate Efficacy in Colitis.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhu Junhong, Jia Huijin, Yi Lanlan, Song Guangyao, Fu Pengfei, Cheng Wenjie, Xie Yuxiao, Shi Wenzhe, Zhao Sumei
Аннотация
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with a rising global incidence. Natural conjugated taurocholic acid (TCA) possesses anti-inflammatory properties and shows potential therapeutic effects against UC, although the underlying mechanisms remain unclear.
METHODS: This study employed an integrative approach-combining network pharmacology, bioinformatics, machine learning, immune infiltration analysis, and molecular docking-to investigate the therapeutic mechanisms of TCA in UC. UC-related gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database, and potential TCA targets were predicted using the Comparative Toxicogenomics Database (CTD) and TargetNet platforms. Differentially expressed genes (DEGs) were identified and analyzed via GO and KEGG enrichment analyses.
RESULTS: Four machine learning algorithms (XGBoost, RF, SVM, and NNet) were used to identify six hub genes (TGM2, MMP9, ABCB1, NOS2, ABCG2, CASP1), which were further validated using an artificial neural network. Immune infiltration analysis with CIBERSORT revealed significant alterations in immune cell populations in UC tissues. Further validation through an artificial neural network model confirmed their predictive ability. The enrichment analysis of the hub genes highlighted their roles in immune-related pathways, while the immune infiltration analysis indicated significant differences in immune cell populations between ulcerative colitis tissues and control tissues. The molecular docking results showed that the binding energies of these six proteins to TCA were lower than -5 kcal/mol, with TGM2 having the strongest binding affinity (-10 kcal/mol). The intervention of TCA on colitis mice could improve the inflammatory response by regulating the expression of the TGM2 gene.
CONCLUSIONS: In conclusion, this study suggests that taurocholate alleviates ulcerative colitis by targeting key genes such as TGM2 and modulating immune-related pathways, providing a novel basis for future therapeutic exploration.
METHODS: This study employed an integrative approach-combining network pharmacology, bioinformatics, machine learning, immune infiltration analysis, and molecular docking-to investigate the therapeutic mechanisms of TCA in UC. UC-related gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database, and potential TCA targets were predicted using the Comparative Toxicogenomics Database (CTD) and TargetNet platforms. Differentially expressed genes (DEGs) were identified and analyzed via GO and KEGG enrichment analyses.
RESULTS: Four machine learning algorithms (XGBoost, RF, SVM, and NNet) were used to identify six hub genes (TGM2, MMP9, ABCB1, NOS2, ABCG2, CASP1), which were further validated using an artificial neural network. Immune infiltration analysis with CIBERSORT revealed significant alterations in immune cell populations in UC tissues. Further validation through an artificial neural network model confirmed their predictive ability. The enrichment analysis of the hub genes highlighted their roles in immune-related pathways, while the immune infiltration analysis indicated significant differences in immune cell populations between ulcerative colitis tissues and control tissues. The molecular docking results showed that the binding energies of these six proteins to TCA were lower than -5 kcal/mol, with TGM2 having the strongest binding affinity (-10 kcal/mol). The intervention of TCA on colitis mice could improve the inflammatory response by regulating the expression of the TGM2 gene.
CONCLUSIONS: In conclusion, this study suggests that taurocholate alleviates ulcerative colitis by targeting key genes such as TGM2 and modulating immune-related pathways, providing a novel basis for future therapeutic exploration.