Blood transcriptomics as CT adjuvant to exclude hemorrhage in acute stroke

什么？我们将测试基于rna-seq的生物标志物分析的准确性，以预测中风的诊断。 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 研究新的测序方法，以加快获得可操作结果(纳米孔)的时间。 为什么？当使用溶栓tPA时，时间至关重要，因为药物必须在3-4.5内给药 中风发作的小时数。在这一时间窗口内越早给予tPA，好处就越大。 此外，必须通过CT扫描排除脑内出血；目前唯一的方法 做出这一治疗上至关重要的决定。放射科医生对CT结果的解释延迟，或缺乏 可用的成像设备是不开始溶栓治疗的最常见原因。。因此， 高度敏感的血液测试的确证使用将使急诊室医生对他们的CT充满信心 在没有放射科医生现场CT读数的情况下进行解释。因此，及时给予tPA将 允许减轻中风负担。因此，一种快速的生物标志物检测方法可以排除急性出血。 中风将减少上门打针的时间，降低死亡率，并改善中风的预后。 中风负担在非裔美国人和女性中较高，但这些人群在 基因组研究。我们通过评估来自单一性别或种族的测试准确性来测试性别和种族的影响 种族，然后在异性或高加索人身上测试。这些实验将决定混血性别 或者，种族来源的测试比来自单一群体的测试更准确。最后，我们调查了 使用新的纳米孔测序技术加快测试速度的方法。 多么?我们在格雷迪纪念医院马库斯中风中心开展的血液生物标记物研究提供了 区分缺血性中风和出血性中风的诊断血液测试。我们不依赖于单人 生物标志物，而是通过使用NEXT对静脉血中的整个转录组(所有RNA)进行分析 代RNA测序。这些数据提供了高度准确的中风诊断、确定中风亚类型 提供强大的结果预测，并按性别显示差异和治疗反应。我们假设 外周血中转录组的差异可以预测出血性与缺血性卒中的CT诊断。我们 建议从格雷迪纪念医院招募患者，并获取血液样本进行RNA测序。 从这个数据集中，我们将测试三个具体目标：目标一：确定血液RNA图谱的准确性 预测CT记录的出血性中风。目的二：确定性别和种族对转录的影响 轮廓精度。目的三：展示快速核糖核酸测量技术识别缺血的准确性 脑出血侧写。 影响：快速的护理点血液测试来诊断中风和中风亚型将增加 符合tPA治疗条件的急性卒中人群，显著降低了卒中发病率和死亡率。

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.