Personalizing EmerGency/Acute therapeuticS Utilizing Systems biology (PEGASUS)

摘要 利用系统生物学实现急诊/急诊个体化治疗的全球目标 (Pegasus)研究计划是为了提高在常见急性护理条件下的药物有效性和安全性。 急诊科对急性疾病的药物治疗仅在25%-60%的病例中有效。的确有 通过在急诊实施精准医学计划来改进急诊治疗的巨大机遇 护理设置。我们将使用电子健康记录中的表型数据，并将该数据链接到 药物基因组和代谢组学数据，以发现药物有效性和安全性的新机制。 最终，临床、基因组和代谢数据将被集成到预测系统生物学模型中，以 提高急症患者的治疗成功率。飞马计划得到了洛奇的支持 山生物库和科罗拉多州个性化医学中心。通过最大化 研究人员早期研究奖(MIRA-ESI)资金公告飞马将 重点关注常见的急性护理情况，如恶心、疼痛和心血管疾病，最终 扩大到更罕见的药物安全状况，如过敏反应和尖端扭力。我们利用 药物代谢酶的多态性，如CYP2D6，作为我们模型的枢纽，并使用生物 急性疾病中存在的扰动，以确定新的途径、机制和相关的遗传变异 在这些常见的情况下，药物的安全性和有效性。在未来，这些模型将被测试 未雨绸缪。这种系统生物学方法在精确医学中的实施将提高药物的质量 在急性情况下的有效性和安全性。

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.