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A new method for prioritizing drug repositioning candidates extracted by literature-based discovery

机译:一种基于文献的发现优先提取药物重新定位候选者的新方法

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Drug repositioning has been a topic of great attention to researchers and pharmaceutical companies due to its significant impact on the cost of drug discovery. There are several approaches to identify potentially novel drug candidates through repurposing. Literature mining has played a critical role in mining such information from scientific articles. In this paper, we used drug-gene and gene-disease semantic predications extracted from Medline abstracts to generate a list of potential drug-disease pairs. We further ranked the generated pairs, by assigning scores based on the predicates that qualify drug-gene and gene-disease relationships. On comparing the top-ranked drug-disease pairs against the Comparative Toxicogenomics Database (CTD), a curated database for drug-disease relations, we found that a significant percentage of top ranked pairs appeared in CTD. Co-occurrence of these high-ranked pairs in Medline abstracts further improves the confidence in our approach to rank the inferred drug-disease relations higher in the list. Finally, manual evaluation of top ten pairs ranked by our approach revealed that nine of them have some biological significance based on expert judgment.
机译:由于药物重新定位对药物开发的成本有重大影响,因此药物重新定位一直是研究人员和制药公司高度关注的话题。有几种方法可以通过重新定位来识别潜在的新型药物候选物。文献挖掘在从科学文章中挖掘此类信息方面发挥了关键作用。在本文中,我们使用了从Medline摘要中提取的药物基因和基因疾病语义谓词来生成潜在药物疾病对的列表。通过基于符合药物基因和基因疾病关系的谓词分配分数,我们进一步对生成的对进行了排名。通过比较排名最高的药物-疾病对与比较药物基因组学数据库(CTD),该数据库是针对药物-疾病关系的精选数据库,我们发现,排名靠前的药物-疾病对中有相当大的百分比出现在CTD中。在Medline摘要中同时出现这些高对词对,可以进一步提高我们对将推断出的药物-疾病关系排在列表中较高位置的方法的信心。最后,根据我们的方法对前十对进行人工评估,发现其中九对具有一定的生物学意义(基于专家判断)。

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