Abstract
Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.
Highlights
Traditional Chinese medicine (TCM) has been practiced over thousands of years in China and other Asian countries for treating various symptoms and diseases [1]
From the TCM-target gene network, it suggests that TCM could be repurposed for various diseases as indicated by the polypharmacology properties of these compounds
From the systems pharmacology-based analysis, we identified artemisinin, an antimalaria drug, that is connected with type 1 diabetes mellitus (q value = 0.11) (Figure 4(b))
Summary
Traditional Chinese medicine (TCM) has been practiced over thousands of years in China and other Asian countries for treating various symptoms and diseases [1]. The drug development process for the modern (or Western) medicine is usually initiated by developing small molecules that target a specific biological target or pathway [2]. In this drug development process, it is much easier to study the mechanism of action (MoA) of these small molecules in a context-specific disease state. Due to the known MoA (e.g., binding to BRAF mutants and inhibiting the downstream signaling pathway) and the target population (e.g., melanoma with BRAF p.V600E), it is much easier to develop predictive biomarker (e.g., BRAF p.V600E) for personalize treatment using modern drug [4]. It remains a challenge to elucidate the molecular mechanisms of a particular TCM in inhibiting biological process in a context-specific disease state because of the “multicomponent, multitarget” nature of TCM
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