TCMATHF:a bioinformatics platform to predict pharmacological action of drug and dynamic molecular changes against from myocardial infarction to heart failure

OBJECTIVE To investigate the characteristics and regulations of medication in different stages of disease by constructing a dynamic disease network and a cellular feature network spanning from myocardial infarction to heart failure.METHODS Based on transcrip⁃tome and single-cell sequencing data from a mouse model of left anterior descending coro⁃nary artery ligation,a dynamic early-middle-late network and cellular feature network were con⁃structed by integrating differential gene expres⁃sion trends and biological functions.The robust⁃ness of the perturbation effect of traditional Chi⁃nese medicine(TCM)on the disease network was calculated based on multi-target TCM,and we acquired the foundational data by analyzing the results of effectiveness.The predictive plat⁃form was scrutinized and assessed with regards to the functional attributes of FDA approveddrugs and compound prescriptions,in order to determine the primary stages of intervention and the drug patterns actions in the progression of heart failure.RESULTS In this study,we devel⁃oped a prediction and analysis platform for assessing the efficacy of drugs using a networkbased approach.The accuracy of the system was validated by FDA approved-drugs.It was found that blood-activating drugs,heat-clearing drugs,and phlegm-expelling drugs exhibited favorable intervention effects during the early to middle stages of the disease by investigating the effects of single herbs and TCM prescriptions on disease progression.Similarly,phlegm-expelling drugs,spirit-nourishing drugs,and diuretic showed better intervention effects during the mid⁃dle to late stages.These findings were consis⁃tent with the clinical use of drugs.Analysis of the clustering heatmap results of TCM prescriptions revealed that the formulas aimed at qi stagnation and blood stasis had a strong effect in early stage,while the formulas for qi and yin deficiency and cardiorenal yang deficiency had a strong effect in the middle to late stages.Furthermore,analysis of the single-cell feature network demon⁃strated that TCM had advantages in modulating the changes in fibroblasts,myofibroblasts,endo⁃thelial cells,and granulocytes during the patho⁃logical process.Additionally,most prescriptions exhibited strong perturbation effects on the fea⁃ture network of NK-T cells,granulocytes,macro⁃phages,and myofibroblasts.CONCLUSION This platform quantitatively evaluates the primary action stages and characteristics of TCM and for⁃mulas involved in the dynamic process of myo⁃cardial infarction to heart failure based on the effective prediction of the efficacy of TCM and FDA approved-drugs.It provides reference for the precise clinical application of TCM and formu⁃las with multiple targets and multiple pathways.