APT: the Analytical Proteomics Team

APT：分析蛋白质组学团队

• 批准号: 7686428
• 负责人: Fred E Regnier
• 金额: $ 4.24万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-28 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686428
• 关键词: Affinity; Antibodies; Biological Markers; Breast; Cancer Detection; Cancer Patient; Consultations; Depth; Detection; Development; Diagnosis; Disease; Eastern Cooperative Oncology Group; Electrospray Ionization; Emerging Technologies; Ensure; Evaluation; Fractionation; Heterogeneity; Human; Immunologics; Indiana; Interferometry; Label; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Medical; Oncology Group; Patients; Proteins; Proteomics; Protocols documentation; Range; Reading; Reagent; Resources; Sampling; Signal Pathway; Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Standards of Weights and Measures; Technology; Universities; base; improved; insight; ion mobility; malignant breast neoplasm; medical schools; nanoscale; sample collection

DESCRIPTION (provided by applicant): Biomarker identification and characterization holds great promise for more precise diagnoses and for tailored therapies. The heterogeneity of human cancers and unmet medical needs in these diseases provides a compelling argument to focus biomarker development in cancer. Mass spectrometry (MS)-based proteomics approaches have provided insight into biomarkers of cancer and other diseases with femtomole sensitivity and high analytical precision, but the results have proven difficult to reproduce owing to the complexity of human biofluids and to the protocols employed in these approaches. This CPTAC proposal will develop robust protocols and standards for MS proteomics employing both electrospray ionization (ESI) and Matrix Assisted Laser Desorption Ionization (MALDI) platforms. Ion mobility MS provides several orders of magnitude increased dynamic range, and protocols for detection of cancer biomarker candidates will be further explored with this emerging technology platform. The consortium will employ high specificity immunologic reagents to develop platforms for precise detection and quantification of biomarkers of relevance for breast and prostate cancer. Immunoaffinity selection of specific biomarker proteins will be achieved as a sample fractionation step using nano-scale immunoaffinity columns prior to MS detection and quantification of specific proteins. An emerging technology incorporating specific antibodies on a microfabricated "bioCD" read by spinning disc interferometry enables label-free evaluation of hundreds of analytes from hundreds of samples in minutes. We will focus on candidate biomarkers relevant for breast and prostate cancer from the NF?B and STATS signaling pathways. Three for-profit and one not-for-profit corporate partners will join several academic groups with deep expertise and extensive resources in proteomics technologies to most efficiently evaluate and roll out robust protocols and standards for MS and affinity proteomics approaches. Prostate cancer samples will be made available from the NCI-sponsored ECOG trial; breast cancer patient and control samples will be collected specifically for this consortium by the Hoosier Oncology Group from throughout the State and region. Standardized sample collection organized from the Indiana University School of Medicine will ensure a diverse cross section of patient demographic groups. Three additional corporate partners will provide key technologies and consultation to improve team efficacy.

描述（由申请人提供）：生物标志物的识别和表征对更精确的诊断和量身定制的疗法有很大的希望。人类癌症的异质性和这些疾病中未满足的医学需求为重点癌症的生物标志物发育提供了令人信服的论点。基于质谱（MS）的蛋白质组学方法为癌症的生物标志物和其他具有替代性的疾病的生物标志物提供了洞察力，但由于人类生物富丽体的复杂性以及在这些方法中采用的方案的复杂性，结果证明很难再现结果。该CPTAC建议将使用电喷雾电离（ESI）和矩阵辅助激光解吸电离（MALDI）平台的MS蛋白质组学制定强大的方案和标准。离子迁移率MS提供了几个数量级增加的动态范围，并且将通过此新兴技术平台进一步探索癌症生物标志物候选者的协议。该财团将采用高特异性免疫学试剂来开发平台，以精确检测和定量乳腺癌和前列腺癌相关性的生物标志物。在MS检测和定量特定蛋白质之前，将使用纳米级免疫亲和力柱作为样品分馏步骤，以作为样品分馏步骤来实现特定生物标志物蛋白的免疫亲和力选择。通过旋转圆盘干涉测量法读取的微观制造“ BioCD”读取的特定抗体的新兴技术可以在几分钟内对数百个样品的数百个分析物进行无标签评估。我们将专注于NF？B和Stats信号通路与乳腺癌和前列腺癌相关的候选生物标志物。三个营利性和一个非营利性公司合作伙伴将与几个具有深厚专业知识和蛋白质组学技术丰富资源的学术团体一起，以最有效地评估和推出MS和亲和力蛋白质组学方法的强大协议和标准。前列腺癌样品将通过NCI赞助的ECOG试验提供；乳腺癌患者和对照样本将由整个州和地区的Hoosier肿瘤学组专门为该财团收集。由印第安纳大学医学院组织的标准化样本收集将确保患者人口组的各种横截面。另外三个公司合作伙伴将提供关键技术和咨询以提高团队效果。