PICquant-An integrated platform for biomarker discovery

描述（由申请人提供）： 尿液是一种容易获得的标本，尚未被很好地用于癌症生物标志物研究。我们已经开发了一种新的稳定同位素质量标签（13 C苯基异氰酸酯，PIC），具有几个优点，在复杂的混合物中的蛋白质定量。我们描述了一个完整的分析平台，尿液生物标志物发现使用PIC标记。该平台包括：1）定制设计的软件（PICquant），用于自动定量标记的峰，2）光谱比较算法，其将光谱分组为代表独特肽家族的光谱注册表，以及3）通过区分CID光谱中的B-和y-离子系列来增强肽测序。完成该平台是一个临床注册表，将采集的标本与当前和前瞻性临床信息（包括结果）联系起来，并使疾病状态与定量蛋白质家族的多变量聚类成为可能。成熟的PICquant平台将提供几乎完全自动化的数据分析，允许将大量患者样本组装成类似于基因表达阵列数据的完整蛋白质丰度谱。此外，扩大注册数据库将用于其他研究人员处理PIC标记或未标记的肽谱。

DESCRIPTION (provided by applicant): Urine is an easily accessed specimen that has not been well exploited for cancer biomarker studies. We have developed a new stable isotope mass tag (13C Phenylisocyanate, PIC) that has several advantages for protein quantification in complex mixtures. We describe a complete analytic platform for urine biomarker discovery using PIC labeling. This platform includes: 1) custom designed software (PICquant) to automatically quantify labeled peaks, 2) a spectrum-comparison algorithm that groups spectra into a Registry of spectra representing unique peptide families, and 3) enhanced peptide sequencing by distinguishing b- and y-ion series in CID spectra. Completing the platform is a clinical registry that links acquired specimens to current and prospective clinical information including outcomes, and that enables multivariate clustering of disease states with quantified protein families. The mature PICquant platform will provide nearly completely automated data analysis, allowing assembly of numerous patient samples into complete protein abundance profiles akin to gene expression array data. Additionally, the expanding Registry database will be of use to other investigators processing either PIC-labeled or unlabeled peptide spectra.