将转录组和有针对性的新方法方法集成到化学生物活性查的分层框架中
Jesse D Rogers1,2, Joseph L Bundy1, Joshua A Harrill1
1Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, North Carolina, USA.
Environmental health perspectives
|May 14, 2025
概括
这项研究表明,将基因表达数据与特定的实验室测试相结合,可以有效地识别化学危险. 这种方法有助于优先考虑化学品进行进一步的安全评估,改进环境风险评估.
科学领域:
- 环境毒理学环境毒理学
- 化学安全评估 化学安全评估
- 分子造型分析 (MOP) 是一种分子造型分析.
背景情况:
- 鉴定化学危险是非常重要的,因为商业和环境中大量的化学品.
- 高通量转录组学 (HTTr) 和受体选试验为改进危险识别提供了潜在的潜力.
研究的目的:
- 将转录组数据与特定的分子点联系起来.
- 为了将转录基因预测与正交受体测定集成在一起,以优先考虑化学危险.
主要方法:
- 在U-2 OS和HepaRG细胞中使用TempO-Seq开发了分子标的基因表达特征.
- 使用HTTr选了1,126种化学物质,并对签名进行了选择性生物活性评估.
- 使用EPA ToxCast数据和潜在受体水平测定验证的预测.
主要成果:
- 在1,126种化学物质中,有201种显示出选择性生物活性;57种被证实是选择性核受体激动剂.
- 转录组签名准确地预测了直角测定生物活性.
- 前性测试证实了49%缺乏先前数据的化学品的预测受体活性.
结论:
- 将转录学与有针对性的直角测试集成在一起,可以支持下一代风险评估.
- 这种分层框架有效地识别了潜在的分子标,并优先考虑化学品进行进一步的测试.
更多相关视频
09:44High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
9.5K
08:31Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
5.0K
相关概念视频
01:26Drug Discovery: Overview
7.7K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.7K
01:28Structure-Activity Relationships and Drug Design
686
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
686