PICquant-An integrated platform for biomarker discovery

描述(由申请人提供)： 尿液是一种容易获取的样本，尚未被很好地用于癌症生物标记物研究。我们开发了一种新的稳定的同位素质量标签(13C苯基异氰酸酯，PIC)，它在复杂混合物中的蛋白质定量方面具有几个优点。我们描述了一个完整的利用PIC标记发现尿液生物标记物的分析平台。该平台包括：1)定制设计的软件(PICquant)，用于自动量化标记的峰；2)光谱比较算法，将光谱分组到代表独特多肽家族的光谱注册表中；以及3)通过区分CID光谱中的b-和y-离子序列来增强多肽测序。完成该平台的是一个临床注册中心，它将获得的样本与当前和预期的临床信息(包括结果)联系起来，并使疾病状态与量化蛋白质家族的多变量聚集成为可能。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，扩展的注册表数据库将对处理PIC标记或未标记的肽谱的其他调查人员有用。

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.