Blood transcriptomics as CT adjuvant to exclude hemorrhage in acute stroke

血液转录组学作为 CT 佐剂排除急性中风出血

• 批准号: 10396630
• 负责人: ROBERT MELLER
• 金额: $ 56.08万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10396630
• 关键词: Accreditation; Adjuvant; Admission activity; Affect; African American; African American population; Alteplase; Biological; Biological Assay; Biological Markers; Blood; Blood Tests; Blood specimen; Brain hemorrhage; Cardiovascular Diseases; Caucasians; Cause of Death; Cerebral hemisphere hemorrhage; Clinical; Collaborations; Data; Data Analyses; Data Set; Diagnosis; Diagnostic; Diagnostic tests; Disease; Emergency Department Physician; Female; Genetic Transcription; Genomics; Goals; Hemorrhage; Hospitals; Hour; Image Analysis; Ischemic Stroke; Joints; Libraries; Measurement; Measures; Methods; Minority Groups; Modeling; Morbidity - disease rate; Morehouse School of Medicine; Needles; Patient Recruitments; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Population; Preparation; RNA; Race; Reading; Recovery; Research; Research Personnel; Risk; Severities; Side; Speed; Stratification; Stroke; Symptoms; Techniques; Technology; Testing; Therapeutic; Thrombolytic Therapy; Time; Universities; Venous; Whole Blood; Woman; X-Ray Computed Tomography; acute stroke; base; diagnostic panel; diagnostic signature; disability; effective therapy; experimental study; gene environment interaction; high risk; imaging facilities; improved; improved outcome; male; mortality; nanopore; next generation; next generation sequencing; novel; outcome prediction; peripheral blood; point of care; point-of-care diagnostics; predictive modeling; programs; radiologist; rapid test; response; secondary analysis; sex; stroke incidence; stroke patient; time use; transcriptome; transcriptome sequencing; transcriptomics; treatment response

What? We will test the accuracy of an RNA-seq based biomarker assay to predict the diagnosis of stroke in a minority population (African American). We will investigate the impact of sex and race on test accuracy, and investigate novel sequencing approaches to speed up the time to obtain actionable results (Nanopores). Why? When using the thrombolytic tPA, time is of the essence, as the drug must be administered within 3-4.5 hrs of stroke onset. The sooner with in this time window that tPA can be administered, the greater the benefit. In addition, intracerebral hemorrhage must have been excluded by CT scanning; currently the sole method to make this therapeutically critical determination. Delays in radiologist interpretation of CT results, or lack of available imaging facilities is the most common reason for thrombolytic treatment not being initiated. . Thus corroborative use of a highly sensitive blood test would permit ER physicians to be confident of their CT interpretation in settings without onsite CT reading by a radiologist. Timely administration of tPA would thereby be permitted reducing stroke burden. Accordingly, a rapid biomarker test to exclude hemorrhage in acute stroke would reduce door to needle times, lower mortality, and improve outcome in stroke. Stroke burden is higher in African Americans and females, yet these populations have lower representation in genomic research. We test the impact of sex and race by assessing test accuracy derived from a single sex or race, and then tested in the opposite sex, or Caucasians. These experiments will determine whether mixed sex or race derived tests are more accurate than those derived from a single population. Finally, we investigate approaches to speed up testing using novel Nanopore sequencing technology. How? Our studies of blood biomarkers, developed at Grady Memorial Hospital Marcus Stroke Center, offers a diagnostic blood test that discriminates between ischemic and hemorrhagic stroke. We do not rely on single biomarkers but rather use analysis of the entire transcriptome (all RNA) in venous blood, by the use of next generation RNA sequencing. These data provide highly accurate stroke diagnosis, determine stroke subtype, offer powerful prediction of outcome, and show differences and treatment response by sex. We hypothesize transcriptome differences in peripheral blood can predict CT diagnosis of hemorrhagic vs. ischemic stroke. We propose to recruit patients from the Grady memorial hospital, and obtain blood samples for RNA sequencing. From this dataset we will test three specific aims: AIM ONE: Determine the accuracy of blood RNA profiles to predict CT documented hemorrhagic stroke. AIM TWO: Determine the effect of sex and race on transcriptomic profile accuracy. AIM THREE: Show the accuracy of rapid RNA measurement techniques to identify ischemic brain hemorrhage profiles. IMPACT: A rapid point of care blood test to diagnosis stroke and stroke subtype will increase the percentage of the acute stroke population eligible for tPA therapy, significantly reducing stroke morbidity and mortality.

什么？我们将测试基于RNA-seq的生物标志物测定的准确性，以预测A中风的诊断 少数民族人口（非裔美国人）。我们将调查性别和种族对测试准确性的影响，以及 研究新型的测序方法，以加快时间以获得可行的结果（纳米孔）。 为什么？当使用溶栓TPA时，时间是本质的，因为该药物必须在3-4.5之内给药。 中风发作的HR。在这个时间窗口中，可以管理TPA，收益越大。 此外，脑部出血必须被CT扫描排除在外。当前是唯一的方法 在治疗上做出关键的决心。放射科医生对CT结果的解释或缺乏 可用的成像设施是未启动溶栓治疗的最常见原因。 。因此 对高度敏感的血液测试的证实使用将使ER医生对他们的CT充满信心 在没有放射科医生的现场阅读的设置中进行解释。及时管理TPA会因此 允许减轻中风负担。因此，快速生物标志物测试可排除急性出血 中风将减少针对针的门，降低死亡率并改善中风的结果。 在非洲裔美国人和女性中，中风负担更高，但这些人群的代表性较低 基因组研究。我们通过评估从单一性别或 种族，然后在异性或高加索人进行测试。这些实验将决定混合性 或种族衍生的测试比单个人群得出的测试更准确。最后，我们调查 使用新型纳米孔测序技术加快测试的方法。 如何？我们对Grady Memorial Hospital Marcus Stroke Center开发的血液生物标志物的研究，提供了一个 诊断血液检查可区分缺血性和出血性中风。我们不依赖单身 生物标志物，而是通过使用下一个对整个转录组（所有RNA）的分析 生成RNA测序。这些数据提供了高度准确的中风诊断，确定中风子类型， 提供有力的结果预测，并通过性别显示差异和治疗反应。我们假设 外周血的转录组差异可以预测出血与缺血性中风的CT诊断。我们 提议从Grady Memorial Hospital招募患者，并获得血液样本进行RNA测序。 从该数据集中，我们将测试三个特定目的：目标：确定血RNA概况的准确性 预测CT记录的出血性中风。目标两个：确定性别和种族对转录组的影响 配置文件准确性。目标三：显示快速RNA测量技术的准确性以鉴定缺血性 脑出血特征。 影响：诊断中风和中风子类型的快速护理血液测试将增加百分比 急性中风人群有资格获得TPA治疗，大大降低了中风的发病率和死亡率。