Inner Mongolia Key Laboratory of Environmental Pollution Control & Waste Resource Reuse, School of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China.
Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, University of Florida, Gainesville, FL, USA.
Comp Biochem Physiol Part D Genomics Proteomics. 2020 Dec;36:100751. doi: 10.1016/j.cbd.2020.100751. Epub 2020 Oct 17.
Proteomics plays a significant role in discerning the effects of chemical exposures in animal taxa. Multi-omics applications have become more pervasive in toxicology, however questions remain about whether proteomics is being utilized by the community to its full potential - are we placing too much stock in transcriptomics and other omics approaches for developing adverse outcome pathways? Proteins are more relevant than transcripts because they are direct mediators of the resulting phenotype. There is also rarely perfect stoichiometry between transcript and protein abundance and transcript abundance may not accurately predict physiologic response. Proteins direct all levels of phenotype: structural proteins dictate physical form, enzymes catalyze biochemical reactions, and proteins act as signaling proteins, antibodies, transporters, ion pumps, and transcription factors to control gene expression. Molecular initiating events (MIEs) of AOPs predominantly occur at the level of the protein (e.g. ligand-receptor binding) and proteomics can elucidate novel MIEs and mapping KEs in AOPs. This critical review highlights the need for proteomics in multi-omics studies in environmental toxicology and outlines steps required for inclusion and wider acceptance in chemical risk assessment. We also present case studies of multi-omics approaches that utilize proteomics and discuss some of the challenges and opportunities for proteomics in comparative ecotoxicology. Our intention is not to minimize the importance of other omics technologies, as each has strengths and limitations, but rather to encourage researchers to consider proteomics-based methods in multi-omics studies and AOP development.
蛋白质组学在辨别化学暴露对动物分类群的影响方面发挥着重要作用。多组学应用在毒理学中变得越来越普遍，然而，关于蛋白质组学是否被该领域充分利用的问题仍然存在——我们是否过于依赖转录组学和其他组学方法来开发不良结局途径？蛋白质比转录物更相关，因为它们是产生表型的直接介质。转录本和蛋白质丰度之间也很少有完美的化学计量关系，并且转录本丰度可能无法准确预测生理反应。蛋白质指导所有层次的表型：结构蛋白决定物理形态，酶催化生化反应，蛋白质作为信号蛋白、抗体、转运蛋白、离子泵和转录因子来控制基因表达。AOP 的分子起始事件（MIEs）主要发生在蛋白质水平（例如配体-受体结合），蛋白质组学可以阐明新的 MIEs 并在 AOP 中映射关键事件。本综述强调了蛋白质组学在环境毒理学多组学研究中的必要性，并概述了在化学风险评估中纳入和更广泛接受所需的步骤。我们还介绍了利用蛋白质组学的多组学方法的案例研究，并讨论了蛋白质组学在比较生态毒理学中的一些挑战和机遇。我们的目的不是贬低其他组学技术的重要性，因为每种技术都有其优势和局限性，而是鼓励研究人员在多组学研究和 AOP 开发中考虑基于蛋白质组学的方法。
