TCMATHF:a bioinformatics platform to pre-dict pharmacological action of drug and dynamic molecular changes against from myocardial infarction to heart failure
10.3867/j.issn.1000-3002.2023.z1.032
- Author:
Yujie XI
1
,
2
;
Xuan TANG
;
Feifei GUO
;
Hongjun YANG
Author Information
1. Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China
2. Beijing Key Laboratory of Tradi-tional Chinese Medicine Basic Research on Pre-vention and Treatment for Major Diseases,Experi-mental Research Center,China Academy of Chi-nese Medical Sciences,Beijing 100700,China
- Keywords:
myocardial infarction;
heart failure;
dynamic network;
single cell;
drug perturbation
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(z1):26-27
- CountryChina
- Language:Chinese
-
Abstract:
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 approved-drugs 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 network-based 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.
