Integrated analysis of protein expression data from the Reverse Phase Protein Array (RPPA) platform

对反相蛋白阵列 (RPPA) 平台的蛋白表达数据进行集成分析

• 批准号: 9789028
• 负责人: Rehan Akbani
• 金额: $ 40.09万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-13 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789028
• 关键词: Algorithms; Award; Back; Biological; Cancer Center; Cancer Patient; Clinical; Communities; Competence; Computer software; Computing Methodologies; Contracts; DNA Methylation; Data; Data Analyses; Data Set; Data Sources; Deposition; Evolution; Excision; Feedback; Future; Galaxy; Genome; Genome Data Analysis Center; Goals; Infrastructure; Intervention; Investigation; Light; Malignant Neoplasms; Maps; Measures; Messenger RNA; Methodology; MicroRNAs; Molecular; Mutation; National Cancer Institute; Outcome; Pathway Analysis; Pathway interactions; Pattern; Performance; Phase; Phosphorylation; Process; Protein Analysis; Protein Array; Proteins; Proteomics; Quality Control; Research; Research Personnel; Running; Sampling; Software Tools; Specific qualifier value; Testing; Work; analysis pipeline; base; bioinformatics tool; biological systems; cancer genomics; cancer initiation; cancer therapy; clinically relevant; computerized tools; data warehouse; design; expectation; file format; improved; innovation; knowledge base; next generation; novel; novel therapeutic intervention; programs; protein expression; repository; secondary analysis; targeted treatment; therapy resistant; tool; tumor; working group

Project Summary/Abstract The National Cancer Institute has initiated, or will initiate, a number of large-scale cancer genomics programs under the aegis of the Center for Cancer Genomics (CCG). The overall goal of those programs is to help elucidate the mechanisms of cancer initiation, evolution, and resistance to therapy through detailed molecular characterization of tumor samples across multiple technological platforms. As most therapy targets are proteins, and protein phosphorylation is functionally important, accurate analysis of protein is critical to the effort. Consequently, MD Anderson was awarded the Genome Characterization Center contract to develop and apply a high-throughput reverse-phase protein array (RPPA) pipeline (Contact PD/PI Gordon Mills; PD/PI Rehan Akbani). The present proposal is for the establishment of a Specialized Genome Data Analysis Center (GDAC) at MD Anderson under the same auspices. As its first objective, the GDAC will directly support CCG projects by analyzing RPPA data for the Analysis Working Groups (AWGs). The GDAC will participate in discussions, solicit feedback from the AWGs, and suggest future directions for research. A second objective of the GDAC will be to enhance its current bioinformatic tools to improve the analysis and interpretation of RPPA data, whether developed under the aegis of the CCG or through other community approaches. Specifically, the aims of the GDAC are to (i) Extract high-quality, analysis-ready protein expression measures from the RPPA data; (ii) Cluster RPPA data and conduct integrated analysis by correlating RPPA data with clinical and other molecular data; (iii) Perform knowledge-based and independent pathway analysis of RPPA data to identify proteomic pathways that have been substantially altered in the set of cases in each CCG project; and (iv) Continue to develop innovative bioinformatic and computational tools and methodologies to improve the RPPA data analysis pipeline. The pipeline will be shared publicly for the benefit of other researchers. The GDAC will perform the stated tasks by continuing to develop a fully or semi-automated software pipeline using the Galaxy software infrastructure and their own software modules. A preliminary version of the pipeline, together with the necessary expertise for systems biological interpretation of the results, is already in place and will be available at the beginning of the performance period. Further enhancements of the pipeline will be implemented as the GDAC progresses. The pipeline will input raw or pre-processed RPPA data from a central data repository that is specified by the CCG; perform quality control; remove any batch effects; analyze the data using novel plus traditional algorithms; correlate the data with other molecular/clinical features; visualize the outcome; and then deposit the results back in the repository for use by the AWG. The GDAC will interact and collaborate with other components of the CCG consortium to discover biologically and clinically relevant findings that will shed light on the underlying mechanisms of cancer and offer potential avenues for novel therapeutic approaches.

项目摘要/摘要 国家癌症研究所已启动或将启动许多大规模的癌症基因组学计划 在癌症基因组学中心（CCG）的宙斯盾下。这些程序的总体目标是帮助 通过详细的分子阐明癌症起步，进化和对治疗的抗药性的机制 跨多个技术平台的肿瘤样品的表征。因为大多数疗法目标是 蛋白质和蛋白质磷酸化在功能上很重要，对蛋白质的准确分析对于 努力。因此，MD Anderson被授予基因组表征中心合同，以开发和 应用高通量反相蛋白阵列（RPPA）管道（接触PD/PI Gordon Mills; PD/PI Rehan Akbani）。目前的建议是建立专业的基因组数据分析中心 （GDAC）在MD Anderson的同一主持下。作为其第一个目标，GDAC将直接支持CCG 通过分析分析工作组（AWG）的RPPA数据来进行项目。 GDAC将参加 讨论，征求AWG的反馈，并提出未来的研究方向。第二个目标 GDAC将是增强其当前的生物信息学工具，以改善RPPA的分析和解释 数据，无论是根据CCG的宙斯盾还是通过其他社区方法开发的数据。 具体而言，GDAC的目的是（i）提取高质量的，分析的蛋白质表达 RPPA数据的措施； （ii）群集RPPA数据并通过将RPPA关联来进行集成分析 具有临床和其他分子数据的数据； （iii）执行基于知识和独立途径分析 RPPA数据的识别蛋白质组学途径，这些途径已在每种情况下都发生了重大改变 CCG项目； （iv）继续开发创新的生物信息学和计算工具和方法论 改善RPPA数据分析管道。该管道将​​公开共享以造福其他 研究人员。 GDAC将继续开发完全或半自动 使用Galaxy软件基础架构及其自己的软件模块的软件管道。初步 管道的版本，以及对结果的系统生物学解释的必要专业知识， 已经到位，将在性能期开始。进一步的增强 随着GDAC的进行，该管道将实施。管道将输入原始或预处理的RPPA 来自CCG指定的中央数据存储库的数据；执行质量控制；删除任何批次 效果；使用新颖的传统算法分析数据；将数据与其他分子/临床相关联 特征;可视化结果；然后将结果放回存储库中，以供AWG使用。这 GDAC将与CCG财团的其他组件进行互动和合作，以在生物学和 临床上相关的发现将阐明癌症的潜在机制并提供潜力 新型治疗方法的途径。