Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry*
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry*
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DOI：
10.1074/mcp.m113.034595
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发表时间：
2014-04-01
影响因子：
7
通讯作者：
Smith, Richard D.
中科院分区：
文献类型：
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作者：
Baker, Erin Shammel;Burnum-Johnson, Kristin E.;Smith, Richard D.
使用比目前采用的侵入性更小、更安全和更临床可接受的方法来快速诊断疾病状态是医学领域的关键方向。虽然基于MS的蛋白质组学方法试图满足这些目标，但诸如临床相关生物流体样品中蛋白质浓度的巨大动态范围以及解决人类生物多样性的需要等挑战已经减缓了它们的应用。在此，我们报告了一种新的仪器平台的使用，该平台通过将快速气相多路离子迁移谱分离技术的进步与液相色谱和MS相结合来解决这些挑战，以大幅提高测量灵敏度和通量，进一步实现未来基于MS的高通量临床应用。液相色谱-离子迁移谱-MS平台的初步应用分析了60例肝移植后复发性纤维化进展患者和60例非移植患者的血清样本，说明了其对疾病表征的潜在效用。
Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.