Université de Paris, Inserm UMR S-1124, 75006 Paris, France.
Toxicol Sci. 2020 Jan 1;173(1):32-40. doi: 10.1093/toxsci/kfz214.
Bisphenol F (BPF) is one of several Bisphenol A (BPA) substituents that is increasingly used in manufacturing industry leading to detectable human exposure. Whereas a large number of studies have been devoted to decipher BPA effects, much less is known about its substituents. To support decision making on BPF's safety, we have developed a new computational approach to rapidly explore the available data on its toxicological effects, combining text mining and integrative systems biology, and aiming at connecting BPF to adverse outcome pathways (AOPs). We first extracted from different databases BPF-protein associations that were expanded to protein complexes using protein-protein interaction datasets. Over-representation analysis of the protein complexes allowed to identify the most relevant biological pathways putatively targeted by BPF. Then, automatic screening of scientific abstracts from literature using the text mining tool, AOP-helpFinder, combined with data integration from various sources (AOP-wiki, CompTox, etc.) and manual curation allowed us to link BPF to AOP events. Finally, we combined all the information gathered through those analyses and built a comprehensive complex framework linking BPF to an AOP network including, as adverse outcomes, various types of cancers such as breast and thyroid malignancies. These results which integrate different types of data can support regulatory assessment of the BPA substituent, BPF, and trigger new epidemiological and experimental studies.
双酚 F（BPF）是双酚 A（BPA）的几种替代品之一，在制造业中的使用越来越广泛，导致人类可检测到的暴露。尽管已经有大量的研究致力于揭示 BPA 的影响，但对其替代品的了解要少得多。为了支持关于 BPF 安全性的决策，我们开发了一种新的计算方法，用于快速探索其毒理学效应的现有数据，结合文本挖掘和综合系统生物学，旨在将 BPF 与不良结局途径（AOP）联系起来。我们首先从不同的数据库中提取了 BPF-蛋白质相互作用的信息，并使用蛋白质-蛋白质相互作用数据集将其扩展到蛋白质复合物中。对蛋白质复合物的过度表达分析允许确定最相关的生物途径，这些途径可能是 BPF 的靶点。然后，使用文本挖掘工具 AOP-helpFinder 对文献中的科学摘要进行自动筛选，结合来自不同来源（AOP-wiki、CompTox 等）的数据集成和手动整理，使我们能够将 BPF 与 AOP 事件联系起来。最后，我们将通过这些分析收集的所有信息结合起来，构建了一个将 BPF 与包括乳腺癌和甲状腺癌等各种癌症在内的 AOP 网络联系起来的综合复杂框架。这些整合了不同类型数据的结果可以支持对 BPA 替代品 BPF 的监管评估，并引发新的流行病学和实验研究。
