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Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

机译：用于解释基因表达数据的下一代文本挖掘介导的化学反应特异性基因集的产生

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Background Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p -values Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Conclusions Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect.
机译：背景技术用于化合物的药理和/或毒性作用预测的基因（基因组）的化学反应特异性列表的可用性有限。我们假设下一代文本挖掘（next-gen TM）可以创建更多的基因集，并且这些可以与基因集分析（GSA）方法一起用于化学治疗鉴定，药理机理阐明和化合物比较毒性概况。方法我们通过下一代TM为人和小鼠创建了30,211个化学反应特异性基因集，并从比较毒物基因组数据库（CTD）中获得了1,189（人）和588（小鼠）基因集。我们测试了显着差异表达（SDE）（错误发现率校正的p值）结果在3个GE数据集中显着改变了与化学处理相匹配的下一代TM衍生基因集，而相应的CTD衍生基因集也显着改变在5个GE数据集中发生了改变，在PPARA基因敲除的GE数据集中显着改变了6个下一代TM衍生的纤维状基因集和4个CTD衍生的纤维状基因集，cMap中的纤维状签名均没有对PPARA GE签名显着评分33。三唑GE数据集中的环境毒物基因组发生了显着变化，其中21种毒物具有与三唑类似的毒性模式，我们证实了胚胎有毒作用，并将三唑与其他化学品区分开来。化学反应特异性基因组是一种可扩展的方法，用于鉴定与其他化学物质的基因反应相似性，从中可以推断出潜在的交流模式和/或毒性作用。

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