REMISE study: REMnant biospecimen Investigation in SEpsis

项目总结/摘要 每年有近200万美国人因败血症住院，近五分之一的人 无法生存。大多数减少脓毒症死亡的努力开始的前提是， 在很大程度上是相似的，并且将治疗靶向单一机制将改善 结果。但是脓毒症患者在病原体、生物学、结果方面不同， 具有治疗反应性内型。对脓毒症内源性的研究越来越多， 受限于昂贵的基础设施和不可扩展的生物样本收集。解决 为了应对这一挑战，我们将使用临床残留物生物储存库来了解可行性， 完整性和对脓毒症机制研究的科学价值。我们将评估传统 生物标志物、定量蛋白质组学、代谢组学、脂质组学和病原体基因组学 对剩余样本进行测序并将成功的数据“层”分级为比例， 社区医院仓库这一跨领域项目将由一个 外部顾问委员会，在炎症，免疫学，计算和 系统生物学、实验室和病理学。这种做法将进一步 发展我们的NIGMS资助的临床转化实验室，创造新的假设 从一个多样化的，学术和社区医院残余生物储存库获得， 败血症患者的内型富集群体。最后，我们将进一步整合 这些数据与严重创伤患者的多组学读数一起探索 共享/非共享机制在危重病中的作用。

PROJECT SUMMARY / ABSTRACT Almost 2 million Americans are hospitalized with sepsis each year, and nearly one in five don’t survive. Most efforts to reduce sepsis deaths begin with the premise that patients are largely similar, and that targeting therapeutics to a single mechanism will improve outcomes. But sepsis patients differ in pathogen, biology, outcomes, and are proposed to have treatment responsive endotypes. Greater study of sepsis endotypes has been limited by costly infrastructure and biospecimen collection that is not scalable. To solve this challenge, we will use a clinical remnant biorepository to understand feasibility, integrity, and scientific value for mechanistic sepsis research. We will evaluate traditional biomarkers, quantitative proteomics, metabolomics, lipidomics, and pathogen genomic sequencing in remnant specimens and graduate successful data “layers” to a scaled, community hospital repository. This cross-cutting project will be supervised by an external advisory board with expertise in inflammation, immunology, computational and systems biology, and laboratory and pathology medicine. This approach will further develop our NIGMS-funded clinical-translational laboratory, creating new hypotheses from a diverse, academic and community hospital remnant biorepository acquired from an endotype-enriched population of sepsis patients. Finally, we will further integrate these data with multi-omics read-outs in severely injured trauma patients to explore shared/unshared mechanisms in critical illness.