Wang Yunfeng, Chen Xiujie, Liu Lei, Chen Yuelong, Ma Hongzhe, Yang Ruizhi, Liu Xiangqiong
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
Mol Biosyst. 2015 Jul;11(7):2060-7. doi: 10.1039/c5mb00242g.
Drug side effects, or adverse drug reactions (ADRs), have become a major public health concern and often cause drug development failure and withdrawal. Some ADRs always occur concomitantly. Therefore, identifying these ADRs and their common molecular basis can better promote their prevention and treatment. In this paper we predicted the potential proteins for ADR pairs with similar mechanisms based on three layers of information: (i) the drug co-occurrence between a pair of ADRs; (ii) the correlation between a protein and an ADR pair based on the co-occurrence of drugs and (iii) the interaction between these proteins within the protein-protein interaction (PPI) network. The methods of randomization and functional annotation are used to investigate and analyze the relation between causative proteins and similar ADR pairs. The prediction accuracy of the relation between similar ADR pairs and related proteins reached 80%, and it increases with the number of drugs shared by the ADR pairs. From the ADR network made of single ADRs from predicted similar ADR pairs, we found that some ADRs are involved in multiple ADR pairs. The functional analysis of these ADR-related proteins suggests that a similar molecular basis is shared by multiple ADR pairs containing the same ADR, and these ADR pairs are almost caused by the same drug sets. The results of this study are reliable and provide a theoretical basis for the better prevention and treatment of ADRs that always occur concomitantly.
药物副作用，即药物不良反应（ADR），已成为一个主要的公共卫生问题，常常导致药物研发失败和撤市。一些不良反应总是同时出现。因此，识别这些不良反应及其共同的分子基础能够更好地促进对它们的预防和治疗。在本文中，我们基于三层信息预测了具有相似机制的不良反应对的潜在蛋白质：（i）一对不良反应之间的药物共现情况；（ii）基于药物共现情况的蛋白质与不良反应对之间的相关性；（iii）蛋白质 - 蛋白质相互作用（PPI）网络中这些蛋白质之间的相互作用。采用随机化和功能注释的方法来研究和分析致病蛋白质与相似不良反应对之间的关系。相似不良反应对与相关蛋白质之间关系的预测准确率达到了80%，并且随着不良反应对共享药物数量的增加而提高。从由预测的相似不良反应对中的单一不良反应构成的ADR网络中，我们发现一些不良反应涉及多个不良反应对。对这些与ADR相关蛋白质的功能分析表明，包含相同不良反应的多个不良反应对共享相似的分子基础，并且这些不良反应对几乎由相同的药物组合引起。本研究结果可靠，为更好地预防和治疗总是同时出现的不良反应提供了理论依据。
