基于组织特异性和直接邻居相似度方法预测疾病–药物关系

Prediction of disease–drug relationships based on tissue specificity and direct neighbor similarity

复杂疾病的致病机理一直是人类健康领域面临的重大难题之一,通过传统的方法进行新药开发,需要大量的时间与金钱,已经满足不了人们的需求.近几年来寻找已知药物新的治疗效果,即药物重定位,已经成为治疗更多疾病的一个有效途径.目前组织特异性的研究已经取得一些成果,但是传统的药物重定位方法很少考虑疾病的组织特异性.本文提出基于组织特异性和直接邻居相似度方法预测药物的新适应症,同时深入探讨考虑疾病的组织特异性对药物重定位研究的影响.首先研究组织特异性的发展及其特点,并提出基于组织特异性数据,应用直接邻居的相似度进行药物重定位研究.从数据库DrugBank中提取11405条已知药物–靶标关系,并从人类孟德尔遗传数据库中获得5种癌症(乳腺癌、结肠癌、肝癌、肺癌、卵巢癌)及其致病基因数据,利用5种癌症对应的组织特异性相互作用网络作为背景网络,基于直接邻居距离度量方法构建25个组织特异性药物–疾病二部网络,实验结果通过CTD (comparative toxicogenomics database)标准数据库进行验证.结果表明,基于组织特异性和直接邻居相似度度量标准会提高药物重定位研究的准确性,为新药的体内和体外实验提供可靠候选集,这也为药物重定位的研究提供了新的思路.

The pathogenesis of complex diseases is a major problem in the field of human health.The development of new drugs through traditional methods requires considerable time and money,which has not met people’s actual requirements.Recently,identifying new therapeutic effects of known drugs via drug repositioning has become an effective way to treat numerous diseases.At present,tissue-specific research has achieved some success;however,traditional drug repositioning methods rarely consider the tissue specificity of the disease.To explore the influence of tissue specificity on drug repositioning studies,this study explores the development of tissue specificity and its characteristics and proposes using direct neighbor similarity in drug repositioning based on tissue-specific data.A total of 11405 known drug–target relationships were extracted from the database DrugBank,and five cancers and their disease-causing gene data were obtained from the human Mendelian genetic database.Through the direct neighbor method and using the tissue-specific interaction network as the background network,five tissue-specific drug–disease bipartite networks were constructed,which provided potential drug–disease associations.The results were verified by the CTD(comparative toxicogenomics database)standard.The experimental results show that the accuracy of drug repositioning studies based on tissue specificity and direct neighbor measurement will provide a reliable candidate set for in vivo and in vitro experiments of new drugs,which also provides new ideas for studying drug repositioning.