title: Advancing the high throughput identification of liver fibrosis protein signatures using multiplexed ion mobility spectrometry.
abstract: 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.
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington;
authors.forename: Erin Shammel
authors.initials: ES
authors.lastname: Baker
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Burnum-Johnson
authors.forename: Jon M
authors.initials: JM
authors.lastname: Jacobs
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Diamond
authors.forename: Roslyn N
authors.initials: RN
authors.lastname: Brown
authors.forename: Yehia M
authors.initials: YM
authors.lastname: Ibrahim
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Orton
authors.forename: Paul D
authors.initials: PD
authors.lastname: Piehowski
authors.forename: David E
authors.initials: DE
authors.lastname: Purdy
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Moore
authors.forename: William F
authors.initials: WF
authors.lastname: Danielson
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Monroe
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Crowell
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Slysz
authors.forename: Marina A
authors.initials: MA
authors.lastname: Gritsenko
authors.forename: John D
authors.initials: JD
authors.lastname: Sandoval
authors.forename: Brian L
authors.initials: BL
authors.lastname: Lamarche
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Matzke
authors.forename: Bobbie-Jo M
authors.initials: BJ
authors.lastname: Webb-Robertson
authors.forename: Brenna C
authors.initials: BC
authors.lastname: Simons
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
authors.forename: Renuka
authors.initials: R
authors.lastname: Bhattacharya
authors.forename: James D
authors.initials: JD
authors.lastname: Perkins
authors.forename: Robert L
authors.initials: RL
authors.lastname: Carithers
authors.forename: Susan
authors.initials: S
authors.lastname: Strom
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Anderson
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
mesh_terms: D002853:Chromatography, Liquid; D006801:Humans; D007477:Ions / Q000737:chemistry; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications* / Q000378:metabolism; D016031:Liver Transplantation; D013058:Mass Spectrometry; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000295:instrumentation / Q000379:methods*
chemical_list: D007477:Ions; D020543:Proteome