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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

基本信息

批准号：
10611988
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
项目类别：
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/10611988
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 Ischemia Brain hemorrhage Cardiovascular Diseases Caucasians Cause of Death Cerebral hemisphere hemorrhage Clinical Collaborations Data Data Analyses Data Set Diagnosis Diagnostic Diagnostic tests Disease Eligibility Determination Emergency Department Physician Exclusion Female Genetic Transcription Genomics Goals Hemorrhage Hospitals Hour Ischemia Ischemic Stroke Joints Libraries Measurement Measures Methods Minority Groups 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 Site Speed Stratification Stroke Symptoms Techniques Technology Testing Therapeutic Thrombolytic Therapy Time Universities Venous Whole Blood Woman X-Ray Computed Tomography acute stroke base cryptogenic stroke data modeling 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 side effect stroke incidence stroke patient transcriptome transcriptome sequencing transcriptomic profiling transcriptomics treatment response

项目摘要

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.

- 你说什么？我们将测试基于RNA-seq的生物标志物测定的准确性，以预测中风的诊断，少数民族（非裔美国人）。我们将调查性别和种族对测试准确性的影响，研究新的测序方法，以加快获得可操作结果的时间（纳米孔）。为什么？为什么？当使用溶栓tPA时，时间是关键，因为药物必须在3-4.5分钟内施用。中风发作的小时数。在这个时间窗内，tPA可以施用得越早，益处越大。此外，必须通过CT扫描排除脑出血;目前唯一的方法，做出这个治疗上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未开始溶栓治疗的最常见原因。.因此高灵敏度血液检查的确证性使用将使急诊室医生对他们的CT有信心在没有放射科医师现场CT阅读的情况下进行解释。及时给予tPA，允许减少中风负担。因此，快速生物标志物测试以排除急性脑出血，中风将减少门到针的时间，降低死亡率，并改善中风的结果。非裔美国人和女性的卒中负担更高，但这些人群在基因组研究我们测试性别和种族的影响，通过评估测试的准确性来自单一性别或种族，然后在异性或高加索人中进行测试。这些实验将决定混合性别或种族衍生的测试比来自单一群体的测试更准确。最后，我们调查使用新的纳米孔测序技术加速测试的方法。怎么做的？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志物研究，提供了一个区分缺血性和出血性中风的诊断性血液检查。我们不依赖单一的生物标志物，而是使用静脉血中的整个转录组（所有RNA）的分析，通过使用下一个 RNA测序。这些数据提供了高度准确的中风诊断，确定中风亚型，提供强有力的结果预测，并显示性别差异和治疗反应。我们假设外周血转录组差异可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病人，并获得血液样本进行RNA测序。从这个数据集，我们将测试三个具体的目标：目的一：确定血液RNA谱的准确性，预测CT记录的出血性卒中。目的二：确定性别和种族对转录组学的影响。轮廓精度。目的三：显示快速RNA测量技术在识别缺血性脑出血特征影响：用于诊断卒中和卒中亚型的快速护理点血液检测将增加适合tPA治疗的急性卒中人群，显著降低卒中发病率和死亡率。