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一种用于评估药物重新利用假设潜力的数据驱动方法。

A data-driven methodology towards evaluating the potential of drug repurposing hypotheses.

作者信息

Prieto Santamaría Lucía, Ugarte Carro Esther, Díaz Uzquiano Marina, Menasalvas Ruiz Ernestina, Pérez Gallardo Yuliana, Rodríguez-González Alejandro

机构信息

Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain.

ETS Ingenieros Informáticos, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain.

出版信息

Comput Struct Biotechnol J. 2021 Aug 9;19:4559-4573. doi: 10.1016/j.csbj.2021.08.003. eCollection 2021.

Abstract

Drug repurposing has become a widely used strategy to accelerate the process of finding treatments. While classical drug development involves high costs, risks, and time-consuming paths, drug repurposing allows to reuse already-existing and approved drugs for new indications. Numerous research has been carried out in this field, both and . Computational drug repurposing methods make use of modern heterogeneous biomedical data to identify and prioritize new indications for old drugs. In the current paper, we present a new complete methodology to evaluate new potentially repurposable drugs based on disease-gene and disease-phenotype associations, identifying significant differences between repurposing and non-repurposing data. We have collected a set of known successful drug repurposing case studies from the literature and we have analysed their dissimilarities with other biomedical data not necessarily participating in repurposing processes. The information used has been obtained from the DISNET platform. We have performed three analyses (at the genetical, phenotypical, and categorization levels), to conclude that there is a statistically significant difference between actual repurposing-related information and non-repurposing data. The insights obtained could be relevant when suggesting new potential drug repurposing hypotheses.

摘要

药物重新利用已成为加速治疗方法寻找过程的一种广泛使用的策略。传统的药物开发成本高、风险大且耗时,而药物重新利用允许将已存在且已获批的药物用于新的适应症。该领域已开展了大量研究。计算药物重新利用方法利用现代异构生物医学数据来识别旧药的新适应症并确定其优先级。在本文中,我们提出了一种全新的完整方法,用于基于疾病-基因和疾病-表型关联来评估新的潜在可重新利用药物,识别重新利用数据和非重新利用数据之间的显著差异。我们从文献中收集了一组已知的成功药物重新利用案例研究,并分析了它们与不一定参与重新利用过程的其他生物医学数据的差异。所使用的信息来自DISNET平台。我们进行了三项分析(在基因、表型和分类水平),得出实际的重新利用相关信息与非重新利用数据之间存在统计学显著差异的结论。在提出新的潜在药物重新利用假设时,所获得的见解可能具有相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f5/8387760/316043722dff/ga1.jpg

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