Omics approaches can monitor responses and alterations of biological pathways at genome-scale, which are useful to predict potential adverse effects by environmental toxicants. However, high throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of “standardized” toxicogenomic methods. Here, a reduced zebrafish transcriptome (RZT) approach was developed to represent the whole transcriptome and to profile bioactivity of chemical and environmental mixtures in zebrafish embryo. RZT gene set of 1637 zebrafish Entrez genes was designed to cover a wide range of biological processes, and to faithfully capture gene-level and pathway-level changes by toxicants compared with the whole transcriptome. Concentration–response modeling was used to calculate the effect concentrations (ECs) of DEGs and corresponding molecular pathways. To validate the RZT approach, quantitative analysis of gene expression by RNA-ampliseq technology was used to identify differentially expressed genes (DEGs) at 32 hpf following exposure to seven serial dilutions of reference chemical BPA (10–10E^–5μM) or each of four water samples ranging from wastewater to drinking water (relative enrichment factors 10–6.4 × 10^–4). The RZT-ampliseq-embryo approach was both sensitive and able to identify a wide spectrum of biological activities associated with BPA exposure. Water quality was benchmarked based on the sensitivity distribution curve of biological pathways detected using RZT-ampliseq-embryo. Finally, the most sensitive biological pathways were identified, including those linked with adverse reproductive outcomes, genotoxicity and development outcomes. RZT-ampliseq-embryo approach provides an efficient and cost-effective tool to prioritize toxicants based on responsiveness of biological pathways.

中文翻译：

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减少转录组方法使用斑马鱼胚胎测试评估环境毒物

Omics方法可以在基因组规模上监测生物途径的反应和改变，这对于预测环境有毒物质的潜在不利影响非常有用。然而，由于高成本和缺乏“标准化”毒物基因组学方法，转录组学在化学评估中的高通量应用受到了限制。在这里，开发了简化的斑马鱼转录组（RZT）方法来代表整个转录组并描述斑马鱼胚胎中化学和环境混合物的生物活性。设计了1637个斑马鱼Entrez基因的RZT基因集，以涵盖广泛的生物学过程，并与整个转录组相比，能够忠实地捕获有毒物质的基因水平和途径水平变化。浓度-响应模型用于计算DEG的作用浓度（EC）和相应的分子途径。为了验证RZT方法，使用RNA-ampliseq技术对基因表达进行定量分析，以鉴定在暴露于七种连续稀释的参考化学BPA（10-10E）后32 hpf下的差异表达基因（DEG）。^-5 μM）或每4个水样从废水到饮用水（相对富集因子10-6.4×10 ^-4）。RZT-ampliseq-embryo方法既灵敏，又能够识别与BPA暴露有关的多种生物活性。根据使用RZT-ampliseq-embryo检测到的生物途径的敏感性分布曲线对水质进行基准测试。最后，确定了最敏感的生物学途径，包括与不良生殖结果，遗传毒性和发育结果相关的那些途径。RZT-ampliseq-embryo方法提供了一种有效且具有成本效益的工具，可以根据生物途径的响应性对毒物进行优先级排序。