TempO-Vseq Screen for Genomic Risk of CAD Using Blood from a Finger Prick
使用手指采血进行 TempO-Vseq 筛查 CAD 基因组风险
基本信息
- 批准号:10080400
- 负责人:
- 金额:$ 40.91万
- 依托单位:
- 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:2020-08-01 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdherenceAffectAgeAge-YearsAmericanAtrial FibrillationBenchmarkingBiological AssayBloodCardiacCardiac healthCause of DeathCessation of lifeClassificationClinicalCoronaryCoronary ArteriosclerosisDNADNA purificationDNA sequencingDataData AnalysesDatabasesDiabetes MellitusDiseaseDropsEarly treatmentEdetic AcidEuropeanEventExhibitsFingersFreezingGenetic Predisposition to DiseaseGenetic RiskGenomicsGenotypeHeart failureIncidenceIschemic StrokeLigationLiteratureMalignant NeoplasmsMeasuresMethodsMyocardial InfarctionNon-Insulin-Dependent Diabetes MellitusPaperPatientsPerformancePersonsPhasePhysiciansProphylactic treatmentReproducibilityRiskRisk AssessmentRisk FactorsSalivaSamplingSampling ErrorsSensitivity and SpecificityShippingShipsSpecificitySudden DeathSwabTechnologyTestingTherapeuticTimeTrainingTubeUtahVariantWhole BloodWomanbasebiobankclinical riskcostdbSNPdisease classificationdisorder riskexperiencegenetic variantgenome wide association studyhealth economicshealthy lifestylehigh riskinnovationinstrumentmenminimally invasivepreventprogramsprophylacticsample collectionscreeningsexsuccesstargeted sequencing
项目摘要
Summary: In this Phase I program we will demonstrate the feasibility of an assay to identify subjects who have
a high genetic risk of coronary artery disease (CAD) and sequelae of angina, myocardial infarction, heart failure
and sudden death using a drop of whole blood spotted on filter paper (WBsf) and assayed directly without
isolation of the DNA using a high throughput TempO-Seq® DNA variant targeted sequencing assay, TempO-
Vseq. The variant calls and genetic risk score (GRS) determined by the TempO-Vseq assay will be benchmarked
against Infinium® genotyping calls and GRS to establish performance. CAD is responsible for 1/3 of deaths in
the US and world-wide. Genetic predisposition for CAD based on a polygenic GRS has been shown to be
independent of conventional risk factors, including age. Large genotyping studies have been carried out that
have shown that a polygenic GRS can predict risk of incident CAD events, and that prophylactic treatment with
statin or adherence to a healthy lifestyle reduces incidence in subjects who are high risk. These studies have
identified the variants that can be targeted to provide a GRS. The clinical rationale for a screening test based on
GRS is that it can be carried out at any age, but if carried out any time before the age of 40, before clinical risk
factors are typically evident, it can identify risk and afford the opportunity for early therapeutic prophylactic use
of statins and/or pursuit of a healthy lifestyle. Both reduce the incidence of CAD, and if statin were to be
prescribed to high-risk GRS subjects, would prevent 1 death for every 13 treated. Having identified the variants
for a CAD screen to determine GRS, the need is for the lowest cost platform that provides the performance of
current genotyping arrays and provides the best health economics of sample collection, shipping, storage, and
assay. Advantages of the TempO-Vseq screen are expected to be 2x or greater reduction in cost, no proprietary
hardware purchase required, simpler sample acquisition from a finger-prick (or if found superior in Phase II,
buccal swab, or spit), simpler shipping and storage of filter paper rather than frozen blood, fully automated
processing and data analysis, lower variant calling error rate than sequencing, and a weekly throughput per
sequencer of >11,000 samples. The same screen augmented with additional variants could be used to identify
high risk for atrial fibrillation (a leading cause of ischemic stroke), type 2 diabetes, and other contributors to CAD.
总结:在这个I期项目中,我们将证明一种检测方法的可行性,
冠状动脉疾病(CAD)和心绞痛、心肌梗死、心力衰竭后遗症的高遗传风险
和猝死,使用一滴全血点在滤纸上(WBsf),并直接测定,
使用高通量TempO-Seq® DNA变体靶向测序测定分离DNA,克里思-
Vseq。将对通过TempO-Vseq测定法确定的变异识别和遗传风险评分(GRS)进行基准测试
根据Infinium®基因分型调用和GRS建立性能。CAD是造成1/3死亡的原因。
美国和全世界。基于多基因GRS的CAD遗传易感性已被证明是
与包括年龄在内的传统风险因素无关。已经进行了大量的基因分型研究,
已经表明,多基因GRS可以预测冠心病事件的发生风险,
他汀类药物或坚持健康的生活方式可降低高危受试者的发病率。这些研究
鉴定了可以靶向提供GRS的变体。筛选试验的临床依据,
GRS是它可以在任何年龄进行,但如果在40岁之前的任何时间进行,
因素通常是明显的,它可以识别风险,并提供机会,早期治疗预防性使用
或者追求健康的生活方式两者都能降低CAD的发病率,如果他汀类药物被用于治疗冠心病,
对于高危GRS受试者,每治疗13例,将预防1例死亡。在确定了这些变体之后,
对于确定GRS的CAD屏幕,需要最低成本的平台,
目前的基因分型阵列,并提供最佳的卫生经济学的样本收集,运输,储存,
比色法TempO-Vseq屏幕的优势预计是成本降低2倍或更大,没有专有的
需要购买硬件,更简单的从手指针刺的样品采集(或者如果在阶段II中发现上级,
口腔拭子或唾液),更简单的运输和储存滤纸,而不是冷冻血液,全自动
处理和数据分析,比测序更低的变异调用错误率,以及每周的吞吐量。
> 11,000个样品的测序仪。增加了其他变体的相同屏幕可用于识别
房颤(缺血性中风的主要原因)、2型糖尿病和其他CAD诱因的高风险。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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{{ truncateString('BRUCE E. SELIGMANN', 18)}}的其他基金
TempO-LINC high throughput high sensitivity single cell gene expression profiling assay Ph II
TempO-LINC 高通量高灵敏度单细胞基因表达谱分析第二阶段
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10699784 - 财政年份:2023
- 资助金额:
$ 40.91万 - 项目类别:
TempO-LINC high throughput, high sensitivity single cell gene expression profiling assay
TempO-LINC 高通量、高灵敏度单细胞基因表达谱分析
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10156786 - 财政年份:2021
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Functional Read-Out Enabling High Compound Throughput Toxicokinetic Assays
功能读出可实现高化合物通量毒代动力学测定
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10080462 - 财政年份:2020
- 资助金额:
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Whole blood filter paper assay for Alzheimers Disease
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10823120 - 财政年份:2019
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TempO-Seq Profiling of RNA Epitranscriptomic Modifications
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TempO-Seq Profiling of RNA Epitranscriptomic Modifications
RNA 表观转录组修饰的 TempO-Seq 分析
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10220107 - 财政年份:2018
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9410000 - 财政年份:2016
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单细胞 II 期多重 mRNA 和 miRNA 分析
- 批准号:
9356539 - 财政年份:2014
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9202942 - 财政年份:2014
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