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Predicting Drug-Drug Interactions Through Large-Scale Similarity-Based Link Prediction

机译:通过大规模的基于相似度的链接预测来预测药物相互作用

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Drug-Drug Interactions (DDIs) are a major cause of preventable adverse drug reactions (ADRs), causing a significant burden on the patients' health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. We present Tiresias, a framework that takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed approach and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs and among newly developed and existing drugs.
机译:药物相互作用(DDI)是可预防的药物不良反应(ADR)的主要原因,给患者的健康和医疗保健系统造成了沉重负担。众所周知,在新药投放市场之前,临床研究无法充分,准确地识别DDI。另外,已知DDI信息的现有公共和专有来源不完整和/或不准确,因此不可靠。结果,出现了关于药物相互作用的计算机内预测的新兴研究机构。我们介绍了Tiresias,这是一个框架,该框架将与毒品有关的数据和知识的各种来源作为输入,并提供DDI预测作为输出。该过程从输入数据的语义集成开始,生成一个知识图,该知识图描述了药物属性以及与各种相关实体(例如酶,化学结构和途径)的关系。然后,该知识图用于在可扩展和分布式框架中计算所有药物之间的几种相似性度量。所得的相似性度量用于构建大型逻辑回归模型的功能,以预测潜在的DDI。我们强调了我们提出的方法的新颖性,并对预测的质量进行了彻底的评估。结果表明,Tiresias在预测现有药物之间以及新开发的药物和现有药物之间的新相互作用方面均有效。

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