Bioinformatics for Protein Microarrays

描述（由申请人提供）：抗体微阵列是一项新兴技术，具有有效和定量分析数千个样品中许多蛋白质的潜力。因此，这项技术可以提供一种急需的机制来确定个体或潜在生物标志物的临床用途。然而，目前，抗体微阵列分析缺乏指导原则、标准程序、经过磨练的实验室实践、基础统计和支持软件，无法大规模产生高质量的结果。因此，我们已经开始开发协议和支持软件（“ProMAT”），专门用于分析蛋白质微阵列数据。该提案的目标是推进抗体微阵列，使其可以用作临床生物标志物验证的常规工具。为了实现这一目标，我们计划建立使用内部和外部标准的新协议，发展在数据收集和分析的各个阶段评估数据质量的统计基础，并开发用于快速数据分析的复杂生物信息学工具，包括先进的质量控制功能。该系统还将有助于识别数据可变性的来源，并允许数据规范化。我们将使用一个迭代过程，通过解决分析要求，推导统计方法和组成原型软件，磨练实验室实践和分析程序，并通过重复实验评估进展，重点是评估数据质量和可重复性。在这项工作完成后，我们将揭示进行抗体微阵列实验的指导原则和要求，并开发一个集成系统，用于快速生成评估生物标志物谱的临床潜力所需的高质量数据。

DESCRIPTION (provided by applicant): Antibody micro arrays are an emerging technology that has the potential to efficiently and quantitatively analyze many proteins in thousands of samples. Therefore, this technology can provide a badly needed mechanism for determining the clinical usefulness of individual or profiles of potential biomarkers. At present, though, antibody micro array analysis lacks the guiding principles, standard procedures, honed laboratory practices, foundational statistics and supporting software to produce quality results on a large scale. Therefore, we have started to develop both the protocols and supporting software ("ProMAT") specifically for analyzing protein micro array data. The goal of this proposal is to advance antibody micro array to the point that it can be used as a routine tool for clinical biomarker validation. To accomplish this goal, we plan to establish novel protocols for the use of internal and external standards, develop the statistical foundation for evaluating data quality at all stages of data collection and analysis, and develop a sophisticated bioinformatics tool for rapid data analysis, including advanced quality control features. This system will also aid in identifying sources of data variability and will allow for data normalization. We will use an iterative process that cycles through resolving assay requirements, deriving statistical methods and composing prototype software, honing laboratory practices and assay procedures, and evaluating progress through repetitive experimentation that focuses on assessing data quality and reproducibility. At the completion of this work, we will have uncovered guiding principles and requirements for conducting antibody micro array experiments and developed an integrated system for rapidly generating the high quality data required to evaluate the clinical potential of biomarker profiles.