The Comprehensive Proteome Characterization Center at Johns Hopkins: High Precision Discovery and Confirmation of Genoproteomic Targets

约翰·霍普金斯大学综合蛋白质组表征中心：基因组蛋白质组目标的高精度发现和确认

• 批准号: 9210931
• 负责人: DANIEL Wanyui CHAN
• 金额: $ 105.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9210931
• 关键词: Advanced Malignant Neoplasm; Affinity; Bioinformatics; Biological; Biological Assay; Biometry; Cancer Biology; Cell Line; Cells; Center for Translational Science Activities; Clinical; Clinical Chemistry; Clinical Research; Collaborations; DNA Sequence Alteration; Data Analyses; Databases; Detection; Development; Differential Diagnosis; Future; Genes; Genomics; Goals; Human; Knowledge; Laboratories; Literature; Malignant Neoplasms; Mass Spectrum Analysis; Microarray Analysis; Molecular; Mutate; Normal tissue morphology; Oncogenes; Pathology; Pathway interactions; Patients; Phosphorylation; Phosphotransferases; Pilot Projects; Post-Translational Protein Processing; Pre-Clinical Model; Principal Investigator; Process; Protein Microchips; Proteins; Proteome; Proteomics; Quality Control; Reproducibility; Research; Research Personnel; Route; Sampling; Science; Scientist; Screening for cancer; Specimen; Technology; Tissues; Translations; Tumor Biology; Work; Xenograft procedure; assay development; base; cancer diagnosis; cancer genomics; cancer type; carcinogenesis; cell transformation; genomic data; glycoproteomics; glycosylation; high throughput technology; improved; meetings; mortality; multidisciplinary; multiple reaction monitoring; oncology; outcome prediction; phosphoproteomics; pre-clinical; precision medicine; precision oncology; programs; proteogenomics; success; technology development; therapeutic target; translational study; tumor; tumor progression

As one of the five current CPTAC PCCs, we propose to leverage our established center to further our research in the comprehensive characterization of biospecimens from human and preclinical models for additional cancer types. We have assembled an outstanding team of basic and clinical scientists to discover and confirm proteins and protein modifications associated with cancer progression using genoproteomic approaches. This multidisciplinary team will be managed by the same three Principal Investigators (PI) and consists of internationally recognized experts in proteomic technologies, genomics, proteogenomics-specific bioinformatics, biostatistics, oncology, pathology, cancer biology, assay development, quality control, technology optimization, and clinical laboratory science/clinical chemistry. Our team has complementary and integrated expertise with previous and ongoing successful collaborations. The plan is to integrate the genomics findings with proteomic analysis (genoproteomics) and to overcome the caveats and challenges in the comprehensive understanding of tumor biology. We believe that genomic data provides a highly valuable molecular route towards the identification of genes and pathways that could be useful for the detection, differential diagnosis, outcome prediction and therapeutic targets of cancer. The proteomic approaches will provide the identification of unique features that are inherent to proteins including post-translational modifications, such as glycosylation and phosphorylation. We propose to use the technology platform validated during the current CPTAC which is high throughput, robust and state of the art. These technologies are proven, with the capability of generating reproducible results across labs. We will use a two-step strategy to characterize defined sets of genomically-characterized samples. The first step is the discovery of target proteins from both biological and clinical specimens using mass spectrometry and affinity based technologies. The second step is the confirmation of these targets using high-throughput, CPTAC Tier 2 analytically validated targeted assays, for example, Multiple Reaction Monitoring Mass Spectrometry (MRM-MS). In addition, we propose to develop pilot studies for technology improvement. The goal is to generate accurate, reproducible, sensitive, quantitative, and multiplexed assays using optimized and standardized high-throughput technologies for the discovered targets. While this PCC application is focused on the proteomic characterization of biological and clinical specimens, we believe that the understanding of and expertise in proteogenomic data analysis and translation will be critical for the success of the PCC and the overall CPTAC network. Investigators/PIs from our proposed PCC will be part of applications for the CPTAC Proteogenomic Data Analysis (PGDAC) and Translational Research (PTCR) Centers. Collaboration and team work are key to the success of the CPTAC program. With this multidisciplinary team of outstanding basic and clinical scientists, our PCC offers the best opportunity for the successful characterization of biological and clinical specimens to discover and confirm cancer targets to advance precision cancer medicine.

作为当前五个CPTAC PCC之一，我们建议利用我们既定的中心来进一步发展我们的研究 在人类和临床前模型的生物测量的全面表征中 类型。我们已经组建了一个杰出的基本和临床科学家团队，以发现和确认蛋白质 和使用基因蛋白质组学方法与癌症进展相关的蛋白质修饰。这 多学科团队将由相同的三名主要研究人员（PI）管理，并由 国际公认的蛋白质组学技术，基因组学，蛋白质组学特异性生物信息学专家， 生物统计学，肿瘤学，病理学，癌症生物学，测定开发，质量控制，技术优化， 和临床实验室科学/临床化学。我们的团队拥有互补和综合的专业知识 以前的和正在进行的成功合作。该计划是将基因组学发现与蛋白质组学相结合 分析（基因蛋白质组学），并克服对全面理解的警告和挑战 肿瘤生物学。我们认为，基因组数据为识别提供了高度有价值的分子途径 基因和途径可能可用于检测，鉴别诊断，结果预测和 癌症的治疗靶标。蛋白质组学方法将提供识别独特功能的识别 是蛋白质固有的，包括翻译后修饰，例如糖基化和磷酸化。 我们建议使用在当前CPTAC中验证的技术平台，该平台很高，稳健 和艺术状态。这些技术已被证明，能够在整个范围内产生可重复的结果 实验室。我们将使用两步策略来表征定义的基因组特征样本集。这 第一步是使用质谱发现从生物学和临床标本中发现靶蛋白 和基于亲和力的技术。第二步是使用高通量的确认这些目标， CPTAC Tier 2分析验证的有针对性测定，例如，多个反应监测质量 光谱法（MRM-MS）。此外，我们建议开发技术改进的试点研究。目标 使用优化和 针对发现的目标的标准化高通量技术。虽然此PCC申请专注于 生物学和临床标本的蛋白质组学表征，我们认为对和 蛋白质组数据分析和翻译方面的专业知识对于PCC的成功和整体至关重要 CPTAC网络。我们提议的PCC的调查人员/PI将成为CPTAC申请的一部分 蛋白质组数据分析（PGDAC）和转化研究（PTCR）中心。协作和团队 工作是CPTAC计划成功的关键。由这个杰出基本和的多学科团队 临床科学家，我们的PCC为成功表征生物学和临床提供了最好的机会 标本发现并确认癌症靶标，以推动精确的癌症医学。