评估多组学整合的性能:甲状腺毒性案例研究。

IF 4.8 2区 医学 Q1 TOXICOLOGY
Sebastian Canzler, Kristin Schubert, Ulrike E Rolle-Kampczyk, Zhipeng Wang, Stephan Schreiber, Hervé Seitz, Sophie Mockly, Hennicke Kamp, Volker Haake, Maike Huisinga, Martin von Bergen, Roland Buesen, Jörg Hackermüller
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引用次数: 0

摘要

多组学数据整合作为系统毒理学和监管风险评估中更全面地涵盖细胞或生物体对化学品暴露的分子反应的前进方向已被反复讨论。在 Canzler 等人(Arch Toxicol 94(2):371-388. https://doi.org/10.1007/s00204-020-02656-y )的文章中,我们回顾了在毒理学研究和化学品风险评估中应用多组学方法的最新进展。我们为多组学研究的实验设计、omics 数据采集以及后续的 omics 数据整合制定了最佳实践。我们发现,针对毒理学研究问题的多组学数据集通常很少见,没有一个数据集包含两个以上的 omics 层,且符合这些最佳实践。由于这些局限性,我们无法全面评估不同数据整合方法的益处,也无法定量评估不同omics层对毒理学研究问题的贡献。在此,我们报告了根据这些最佳实践进行的甲状腺毒性多组学研究。在一项为期 28 天加 14 天恢复期的大鼠口服毒性研究中,我们通过丙基硫脲嘧啶(PTU)和苯妥英分别诱导了直接和间接的甲状腺毒性。我们从血浆、甲状腺和肝脏中收集了临床和组织病理学数据以及六个组学层,包括长短转录组、蛋白质组、磷酸蛋白组和代谢组。我们证明,多组学方法在检测调控通路水平的反应方面优于单组学方法。我们还展示了将组学数据与临床和组织病理学参数相结合是如何促进数据解读的。此外,我们还说明了多组学整合如何暗示非编码 RNA 参与转录后调控。此外,我们还展示了多组学如何促进分组,并评估了单个组学层和组合组学层为这种方法贡献了多少信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluating the performance of multi-omics integration: a thyroid toxicity case study.

Multi-omics data integration has been repeatedly discussed as the way forward to more comprehensively cover the molecular responses of cells or organisms to chemical exposure in systems toxicology and regulatory risk assessment. In Canzler et al. (Arch Toxicol 94(2):371-388. https://doi.org/10.1007/s00204-020-02656-y ), we reviewed the state of the art in applying multi-omics approaches in toxicological research and chemical risk assessment. We developed best practices for the experimental design of multi-omics studies, omics data acquisition, and subsequent omics data integration. We found that multi-omics data sets for toxicological research questions were generally rare, with no data sets comprising more than two omics layers adhering to these best practices. Due to these limitations, we could not fully assess the benefits of different data integration approaches or quantitatively evaluate the contribution of various omics layers for toxicological research questions. Here, we report on a multi-omics study on thyroid toxicity that we conducted in compliance with these best practices. We induced direct and indirect thyroid toxicity through Propylthiouracil (PTU) and Phenytoin, respectively, in a 28-day plus 14-day recovery oral rat toxicity study. We collected clinical and histopathological data and six omics layers, including the long and short transcriptome, proteome, phosphoproteome, and metabolome from plasma, thyroid, and liver. We demonstrate that the multi-omics approach is superior to single-omics in detecting responses at the regulatory pathway level. We also show how combining omics data with clinical and histopathological parameters facilitates the interpretation of the data. Furthermore, we illustrate how multi-omics integration can hint at the involvement of non-coding RNAs in post-transcriptional regulation. Also, we show that multi-omics facilitates grouping, and we assess how much information individual and combinations of omics layers contribute to this approach.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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