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Title: Toward Plasma Proteome Profiling with Ion Mobility-Mass Spectrometry

Journal Article · · Journal of Proteome Research, 5(11):2977-2984
DOI:https://doi.org/10.1021/pr060232i· OSTI ID:894842

Differential, functional, and mapping proteomic analyses of complex biological mixtures suffer from a lack of component resolution. Here we describe the application of ion mobility-mass spectrometry (IMSMS) to this problem. With this approach, components that are separated by liquid chromatography are dispersed based on differences in their mobilities through a buffer gas prior to being analyzed by MS. The inclusion of the gas-phase dispersion provides more than an order of magnitude enhancement in component resolution at no cost to data acquisition time. Additionally, the mobility separation often removes high-abundance species from spectral regions containing low-abundance species, effectively increasing measurement sensitivity and dynamic range. Finally, collision-induced dissociation of all ions can be recorded in a single experimental sequence while conventional MS methods sequentially select precursors. The approach is demonstrated in a single, rapid (3.3 h) analysis of a plasma digest sample where abundant proteins have not been removed. Protein database searches have yielded 731 high confidence peptide assignments corresponding to 438 unique proteins. Results have been compiled into an initial analytical map to be used -after further augmentation and refinement- for comparative plasma profiling studies.

Research Organization:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
894842
Report Number(s):
PNNL-SA-52232; 400412000; TRN: US200702%%428
Journal Information:
Journal of Proteome Research, 5(11):2977-2984, Journal Name: Journal of Proteome Research, 5(11):2977-2984
Country of Publication:
United States
Language:
English