论文标题

网络医学框架揭示了传统中药的通用草药症

Network medicine framework reveals generic herb-symptom effectiveness of Traditional Chinese Medicine

论文作者

Gan, Xiao, Shu, Zixin, Wang, Xinyan, Yan, Dengying, Li, Jun, ofaim, Shany, Albert, Réka, Li, Xiaodong, Liu, Baoyan, Zhou, Xuezhong, Barabási, Albert-László

论文摘要

中医(TCM)依靠天然医疗产品来治疗症状和疾病。虽然临床数据证明了选定的基于TCM的治疗的有效性,但TCM草药治疗疾病的机理根源仍然很大。更重要的是,当前的方法集中于单一草药或处方,缺少TCM的高级一般原则。为了在系统级别上揭示TCM的机械性质,在这项工作中,我们从人类蛋白质Interactome为TCM建立了通用网络医学框架。应用我们的框架揭示了症状(疾病)和TCM中的草药之间的网络模式。我们首先观察到,与症状相关的基因并非随机分布在相互作用组中,而是将其聚集到局部模块中。此外,两个症状模块之间的短网络距离表明症状的同时出现和相似性。接下来,我们表明,草药靶标与症状模块的网络接近可预测草药在治疗症状方面的有效性。我们通过现实世界中医院患者数据来验证我们的框架,以表明(1)住院症状之间的网络距离较短,与较高的相对风险(同时出现)相关,并且(2)草药治疗后患者的症状恢复率指示患者的症状。最后,我们确定了新型的Herb-symptom对,其中草药在治疗症状的有效性由网络预测并在医院数据中得到证实,但以前是TCM社区未知的。这些预测突出了我们框架创造药草发现或重新利用机会的潜力。总之,Network Medicine提供了一个强大的新颖平台,以了解传统医学机制并预测针对疾病的新草药治疗。

Traditional Chinese medicine (TCM) relies on natural medical products to treat symptoms and diseases. While clinical data have demonstrated the effectiveness of selected TCM-based treatments, the mechanistic root of how TCM herbs treat diseases remains largely unknown. More importantly, current approaches focus on single herbs or prescriptions, missing the high-level general principles of TCM. To uncover the mechanistic nature of TCM on a system level, in this work we establish a generic network medicine framework for TCM from the human protein interactome. Applying our framework reveals a network pattern between symptoms (diseases) and herbs in TCM. We first observe that genes associated with a symptom are not distributed randomly in the interactome, but cluster into localized modules; furthermore, a short network distance between two symptom modules is indicative of the symptoms' co-occurrence and similarity. Next, we show that the network proximity of a herb's targets to a symptom module is predictive of the herb's effectiveness in treating the symptom. We validate our framework with real-world hospital patient data by showing that (1) shorter network distance between symptoms of inpatients correlates with higher relative risk (co-occurrence), and (2) herb-symptom network proximity is indicative of patients' symptom recovery rate after herbal treatment. Finally, we identified novel herb-symptom pairs in which the herb's effectiveness in treating the symptom is predicted by network and confirmed in hospital data, but previously unknown to the TCM community. These predictions highlight our framework's potential in creating herb discovery or repurposing opportunities. In conclusion, network medicine offers a powerful novel platform to understand the mechanism of traditional medicine and to predict novel herbal treatment against diseases.

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