Laboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Molecules. 2021 May 26;26(11):3178. doi: 10.3390/molecules26113178.
Human skin aging is affected by various biological signaling pathways, microenvironment factors and epigenetic regulations. With the increasing demand for cosmetics and pharmaceuticals to prevent or reverse skin aging year by year, designing multiple-molecule drugs for mitigating skin aging is indispensable. In this study, we developed strategies for systems medicine design based on systems biology methods and deep neural networks. We constructed the candidate genomewide genetic and epigenetic network (GWGEN) via big database mining. After doing systems modeling and applying system identification, system order detection and principle network projection methods with real time-profile microarray data, we could obtain core signaling pathways and identify essential biomarkers based on the skin aging molecular progression mechanisms. Afterwards, we trained a deep neural network of drug-target interaction in advance and applied it to predict the potential candidate drugs based on our identified biomarkers. To narrow down the candidate drugs, we designed two filters considering drug regulation ability and drug sensitivity. With the proposed systems medicine design procedure, we not only shed the light on the skin aging molecular progression mechanisms but also suggested two multiple-molecule drugs for mitigating human skin aging from young adulthood to middle age and middle age to old age, respectively.
人类皮肤衰老受多种生物信号通路、微环境因素和表观遗传调控的影响。随着化妆品和药品行业对预防或逆转皮肤衰老的需求逐年增加，设计多种分子药物来缓解皮肤衰老变得不可或缺。在这项研究中，我们基于系统生物学方法和深度神经网络开发了系统医学设计策略。我们通过大数据挖掘构建候选全基因组遗传和表观遗传网络（GWGEN）。在对系统进行建模并应用系统识别、系统阶次检测和基于实时谱微阵列数据的主要网络投影方法之后，我们可以根据皮肤衰老的分子进展机制获得核心信号通路并识别关键生物标志物。之后，我们预先训练了一个药物-靶点相互作用的深度神经网络，并应用它根据我们识别的生物标志物来预测潜在的候选药物。为了缩小候选药物的范围，我们设计了两个考虑药物调控能力和药物敏感性的过滤器。通过提出的系统医学设计程序，我们不仅阐明了皮肤衰老的分子进展机制，还分别为从青年到中年以及从中年到老年的皮肤衰老缓解提出了两种多分子药物。
