Personalizing EmerGency/Acute therapeuticS Utilizing Systems biology (PEGASUS)

利用系统生物学 (PEGASUS) 个性化紧急/急性治疗

• 批准号: 10242868
• 负责人: Andrew Albert Monte
• 金额: $ 38.88万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242868
• 关键词: Accident and Emergency department; Acute; Adverse drug event; Anaphylaxis; Award; Biological; CYP2D6 gene; Cardiovascular Diseases; Clinical; Colorado; Data; Effectiveness; Electronic Health Record; Emergency Situation; Enzymes; Funding; Future; Genetic Polymorphism; Genomics; Health Care Costs; Link; Modeling; Nausea; Pain; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacogenomics; Pharmacotherapy; Research; Research Personnel; Safety; Systems Biology; Therapeutic; Torsades de Pointes; acute care; biobank; genetic variant; improved; individual patient; medication safety; metabolomics; patient variability; personalized medicine; phenotypic data; precision medicine; programs; prospective test; public health relevance; success

Abstract The global objective of the Personalizing EmerGency/Acute therapeuticS Utilizing Systems biology (PEGASUS) Research Program is to improve drug effectiveness and safety in common acute care conditions. Drug therapy for acute conditions in the emergency department is only effective in 25-60% of cases. There is tremendous opportunity to improve acute therapeutics by implementing precision medicine programs in acute care settings. We will use phenotypic data from our electronic health record and link this data to pharmacogenomic and metabolomic data to discover new mechanisms of drug effectiveness and safety. Ultimately clinical, genomic, and metabolomic data will be integrated into predictive systems biology models to improve therapeutic success in acutely ill patients. The PEGASUS program is supported by the Rocky Mountain Biorepository and the Colorado Center for Personalized Medicine. Through the Maximizing Investigators' Research Award for Early Stage Investigators (MIRA-ESI) funding announcement PEGASUS will focus on common acute care conditions such as nausea, pain, and cardiovascular disease with eventual expansion to more uncommon drug safety conditions such as anaphylaxis and torsades de pointes. We utilize polymorphism in drug metabolizing enzymes, such as CYP2D6, as the hub of our models and use the biologic perturbations present in acute illness to identify new pathways, mechanisms, and genetic variants associated with drug safety and effectiveness in these common conditions. In the future, these models will be tested prospectively. Implementation of this systems biology approach to precision medicine will improve drug effectiveness and safety in acute conditions.

摘要 利用系统生物学的个性化紧急/急性治疗的全球目标 （PEGASUS）研究计划旨在提高药物在常见急性护理条件下的有效性和安全性。 在急诊室进行的急性疾病药物治疗仅在25-60%的病例中有效。有 通过在急性疾病中实施精准医学计划来改善急性治疗的巨大机会 护理设置。我们将使用电子健康记录中的表型数据，并将这些数据与 药物基因组学和代谢组学数据，以发现药物有效性和安全性的新机制。 最终，临床、基因组和代谢组学数据将被整合到预测系统生物学模型中， 提高急性病患者治疗成功率。PEGASUS计划由Rocky提供支持 山地生物储存库和科罗拉多个性化医疗中心。通过最大化 早期研究者研究奖（MIRA-ESI）资金公告PEGASUS将 重点关注常见的急性护理状况，如恶心、疼痛和心血管疾病， 扩展到更不常见的药物安全性状况，如过敏反应和尖端扭转型室性心动过速。我们利用 药物代谢酶的多态性，如CYP 2D 6，作为我们模型的中心，并使用生物 急性疾病中存在的干扰，以确定新的途径，机制和相关的遗传变异 药物的安全性和有效性。未来，这些车型将接受测试 前瞻性地。将这种系统生物学方法应用于精准医学将改善药物 在急性条件下的有效性和安全性。

项目成果

Genetic variants associated with ALT elevation from therapeutic acetaminophen.

• DOI: 10.1080/15563650.2022.2117053
• 发表时间: 2022-11
• 期刊: CLINICAL TOXICOLOGY
• 影响因子: 3.3
• 作者: Monte, Andrew A.;Mackenzie, Ian Arriaga;Pattee, Jack;Kaiser, Sasha;Willems, Emileigh;Rumack, Barry;Reynolds, Kate M.;Dart, Richard C.;Heard, Kennon J.
• 通讯作者: Heard, Kennon J.