Quantitative technology of Traditional Chinese Medicine concept based on DNA methylation and its application in aging and disease prediction
Jianghui Xiong
Deepome. Inc. Beijing 100193, China
Correspondence: Prof. Jianghui Xiong (Xiongjh77@163.com)
It is generally accepted that Traditional Chinese Medicine is a theoretical system completely different from modern medicine. Here we mapped the concept of yin,yang and 5 organs (heart,liver,spleen,lung,kidney) into gene network by data mining of herbs database annotated by these TCM concepts.We found that herb sets annotated by term yang selectively targeting to pathways that related to the first line response to environmental stress, and the term yin for the structure and function remodeling for raising the intrinsic capacity of the bodies. 5 organs are also selectively targeting to a network of signaling and metabolic pathways. We propose a new concept semo (selective remodeling of pathways),to quantify the potential effect of the combination of yinyang and 5 organs term such as shen yang xu (kidney yang deficiency).In a genome wide DNA methylation profiling data from 656 individuals, we demonstrated that Semo-based features could predict age with correlation coefficient of 0.95 and the proportion of variance of age explained by the model is 0.88. In a genome wide DNA methylation profiling data on Alzheimers disease (n=632), the signatures of super pathway defined by TCM concept could predict disease risk. We propose that the capability medicine which combines principles and approaches of TCM and modern systems biology, holding the promise to shift the paradigm of the research of aging,health and diseases.
一般认为，中医学是一个与现代医学完全不同的理论体系。在这里，我们通过对这些中医概念注释的草药数据库进行数据挖掘，将阴阳和五脏（心、肝、脾、肺、肾）的概念映射到基因网络中。我们发现，以“阳”一词为注释的草药组选择性地针对与环境应激的一线反应相关的路径，而“阴”一词则针对结构和功能重塑，以提高身体的内在能力。五脏也有选择性地针对信号和代谢途径网络。我们提出了一个新概念semo(selective remodeling of pathways)，以量化阴阳五脏概念，如肾阳虚（肾阳虚证）组合的潜在影响。利用全基因组DNA甲基化数据+Semo计算，我们建立了一个精准的甲基化年龄预测模型，相关系数0.95，R方0.88。一组Semo属性可以成功预测阿尔茨海默症风险，其中“肺阳虚”对应的Semo属性预测疾病的Odds ratio为1.74。中医演绎法思维+现代科学精准定量，有望改变衰老、健康和疾病的研究范式。
http://dx.doi.org/10.13140/RG.2.2.19710.05445
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