Combined tissue and fluid proteomics with Tandem Mass Tags to identify low-abundance protein biomarkers of disease in peripheral body fluid: An Alzheimer's Disease case study

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• 作者：Claire L. Russell ; Amanda Heslegrave ; Vikram Mitra ; Henrik Zetterberg ; Jennifer M. Pocock ; Malcolm A. Ward and Ian Pike
• 刊名：Rapid Communications in Mass Spectrometry
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：31
• 期：2
• 页码：153-159
• 全文大小：415K
• ISSN：1097-0231

文摘

Ideal biomarkers are present in readily accessible samples including plasma and cerebrospinal fluid (CSF), and are directly derived from diseased tissue, therefore likely to be of relatively low abundance. Traditional unbiased proteomic approaches for biomarker discovery have struggled to detect low-abundance markers due to the high dynamic range of proteins, the predominance of hyper-abundant proteins, and the use of data-dependent acquisition mass spectrometry (MS). To overcome these limitations and improve biomarker discovery in peripheral fluids, we have developed TMTcalibrator™; a novel MS workflow combining isobarically labelled diseased tissue digests in parallel with an appropriate set of labelled body fluids to increase the chance of identifying low-abundance, tissue-derived biomarkers.