Differential Capture Proteomics for Cardiovascular Disease Biomarker Discovery

用于心血管疾病生物标志物发现的差异捕获蛋白质组学

• 批准号: 7611477
• 负责人: Paul Stroobant
• 金额: $ 20.2万
• 依托单位: DIFFERENTIAL PROTEOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611477
• 关键词: Accounting; Affinity; Antibodies; Antigens; Bacteriophages; Binding; Biological; Biological Assay; Biological Markers; Biological Models; Blinded; Cardiovascular Diseases; Cessation of life; Clinical; Diagnosis; Diagnostic tests; Disease; Drug Formulations; Early Diagnosis; Generations; Goals; Heart Diseases; Human; Immobilization; Immunoassay; Knowledge; Laboratories; Lead; Legal patent; Libraries; Ligands; Liquid substance; Mass Spectrum Analysis; Modeling; Molecular; Monitor; Monoclonal Antibodies; Pan Genus; Patients; Peptide Phage Display Library; Peptides; Phage Display; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Plasma; Plasma Proteins; Process; Proteins; Proteomics; Protocols documentation; Public Health; Reagent; Sampling; Screening procedure; Source; Specificity; Stroke; Surface; System; Technology; Testing; Therapeutic; Time; United States; Validation; Work; base; cardiovascular disorder therapy; commercialization; cost; improved; innovation; interest; novel; outcome forecast; programs; public health relevance; response; success; verification and validation

DESCRIPTION (provided by applicant): In the United States, cardiovascular disease (CVD) accounts for approximately 1.4 million deaths annually, representing nearly 40% of all deaths. The projected cost of heart disease and stroke for 2007 is $431.8 billion. The discovery of new biomarkers will be critical for much-needed advances in screening, diagnosis, prognosis, prediction of therapeutic response and therapeutic monitoring for this devastating disease. The goal for Phase I of this Project is to optimize in human plasma a new proteomics technology, Differential Capture ProteomicsTM (DCP), which can identify the differences in protein composition between two biological samples. This technology also simultaneously creates affinity reagents for each of the identified difference proteins. A patent for DCP has been issued to Differential Proteomics Inc. The goal for a subsequent Phase II study is to apply DCP, newly optimized for human plasma, to the discovery of biomarkers of CVD using appropriate patient [plasma] samples to enable novel protein isolation and identification, novel affinity reagent creation, assay formulation, and clinical validation. Studies in our laboratory to optimize the DCP technology have successfully focused on a model system. However, the capabilities of DCP for CVD biomarker discovery in patient plasma samples have yet to be demonstrated with an optimization study. Such a study is proposed here, in which doped CVD biomarkers (representing a model CVD patient sample) will be tested for detectability at clinical sample level concentrations. The proposed study will use five specific CVD protein antigens, for which there are commercially available immunoassays. The success of this Phase I study will lead to a Phase II program for testing multiple CVD patient [plasma] samples for novel biomarker discovery, assay generation, and validation. Specific Aim 1: Confirm that three pooled Random Peptide Phage Libraries actually contain binding phage species against each of the five CVD antigens chosen. Specific Aim 2: Show how well Differential Capture Proteomics detects the differences between two human plasma samples, one of which is doped with the mixture of five CVD antigens. Specific Aim 3: Establish the specificity of the affinity capture reagents that are generated as part of the process. PUBLIC HEALTH RELEVANCE: Since Differential Capture Proteomics will be significantly more cost- and time-effective than current approaches, it potentially offers a breakthrough system for the integrated discovery, verification, and validation of biomarkers. The discovery of new biomarkers of cardiovascular disease will be critical for much-needed advances in screening, diagnosis, prognosis, prediction of therapeutic response and therapeutic monitoring for this devastating disease.

描述(申请人提供)：在美国，心血管疾病(CVD)每年造成约140万人死亡，占所有死亡人数的近40%。2007年心脏病和中风的预计成本为4318亿美元。新生物标志物的发现将对这种毁灭性疾病的筛查、诊断、预后、治疗反应预测和治疗监测方面亟需的进展至关重要。该项目第一阶段的目标是在人类血浆中优化一种新的蛋白质组学技术-差异捕获蛋白质组分TM(DCP)，该技术可以识别两个生物样本之间的蛋白质组成差异。这项技术还可以同时为每个已识别的差异蛋白创建亲和试剂。DCP的一项专利已经颁发给Differential蛋白质组学公司。后续第二阶段研究的目标是应用新为人类血浆优化的DCP，使用适当的患者[血浆]样本来发现心血管疾病的生物标记物，以实现新的蛋白质分离和鉴定、新的亲和试剂的创建、分析配方和临床验证。我们实验室对DCP技术的优化研究已经成功地集中在一个模型系统上。然而，DCP在患者血浆样本中发现CVD生物标记物的能力尚未得到优化研究的证实。这里提出了这样一项研究，其中掺杂的CVD生物标记物(代表模型CVD患者样本)将在临床样本水平上进行可检测性测试。拟议的研究将使用五种特定的CVD蛋白抗原，对于这些抗原，有商业上可用的免疫分析方法。这项第一阶段研究的成功将导致第二阶段计划，测试多个CVD患者[血浆]样本，以发现、分析和验证新的生物标记物。具体目标1：确认三个随机肽噬菌体文库实际上包含针对所选五种心血管疾病抗原的结合噬菌体物种。具体目标2：展示差异捕获蛋白质组学如何很好地检测两个人类血浆样本之间的差异，其中一个样本掺杂了五种心血管疾病抗原的混合物。具体目标3：确定作为该过程一部分产生的亲和捕获试剂的特异性。公共卫生相关性：由于差异捕获蛋白质组学将比目前的方法更具成本和时间效益，它可能为生物标志物的综合发现、验证和验证提供一个突破性的系统。心血管疾病新生物标志物的发现将对这一毁灭性疾病的筛查、诊断、预后、治疗反应预测和治疗监测方面亟需的进展至关重要。