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Title: Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations

Journal Article · · Proteomics

Proteomic measurements with greater throughput, sensitivity and additional structural information enhance the in-depth characterization of complex mixtures and targeted studies with additional information and higher confidence. While liquid chromatography separation coupled with mass spectrometry (LC-MS) measurements have provided information on thousands of proteins in different sample types, the additional of another rapid separation stage providing structural information has many benefits for analyses. Technical advances in ion funnels and multiplexing have enabled ion mobility separations to be easily and effectively coupled with LC-MS proteomics to enhance the information content of measurements. Finally, herein, we report on applications illustrating increased sensitivity, throughput, and structural information by utilizing IMS-MS and LC-IMS-MS measurements for both bottom-up and top-down proteomics measurements.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC05-76RL01830; R01ES022190; P41 GM103493; P41 GM104603
OSTI ID:
1212228
Report Number(s):
PNNL-SA-107785; 48135; 48203; 400412000
Journal Information:
Proteomics, Vol. 15, Issue 16; ISSN 1615-9853
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 46 works
Citation information provided by
Web of Science

References (53)

Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements journal May 2014
Ion mobility spectrometry—mass spectrometry performance using electrodynamic ion funnels and elevated drift gas pressures journal July 2007
High-resolution separations and improved ion production and transmission in metabolomics journal March 2008
Ion Mobility Measurements of Nondenatured 12–150 kDa Proteins and Protein Multimers by Tandem Differential Mobility Analysis–Mass Spectrometry (DMA-MS) journal January 2011
Protein biomarker discovery and validation: the long and uncertain path to clinical utility journal August 2006
Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation journal November 2010
Cooperative Stabilization of Transthyretin by Clusterin and Diflunisal journal December 2014
Combined Ion Mobility/Time-of-Flight Mass Spectrometry Study of Electrospray-Generated Ions journal October 1997
A targeted proteomics–based pipeline for verification of biomarkers in plasma journal June 2011
Toward Plasma Proteome Profiling with Ion Mobility-Mass Spectrometry journal November 2006
Hadamard Transform Time-of-Flight Mass Spectrometry: More Signal, More of the Time journal January 2003
Evaluation of SDS depletion using an affinity spin column and IMS-MS detection journal September 2012
Skyline: an open source document editor for creating and analyzing targeted proteomics experiments journal February 2010
Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry journal January 2014
Gas-Phase Unfolding and Disassembly Reveals Stability Differences in Ligand-Bound Multiprotein Complexes journal April 2009
Gas-phase separations of protease digests journal November 1998
Metrics for the Human Proteome Project 2013–2014 and Strategies for Finding Missing Proteins journal December 2013
Dynamically Multiplexed Ion Mobility Time-of-Flight Mass Spectrometry journal August 2008
Utilizing Human Blood Plasma for Proteomic Biomarker Discovery journal August 2005
Ion Mobility Derived Collision Cross Sections to Support Metabolomics Applications journal March 2014
NWChem: A comprehensive and scalable open-source solution for large scale molecular simulations journal September 2010
Electrospray ionization with ambient pressure ion mobility separation and mass analysis by orthogonal time-of-flight mass spectrometry journal January 2001
Phenotypic Mapping of Metabolic Profiles Using Self-Organizing Maps of High-Dimensional Mass Spectrometry Data journal June 2014
Expression, purification, and in vitro cysteine-10 modification of native sequence recombinant human transthyretin journal June 2007
A novel approach to collision-induced dissociation (CID) for ion mobility-mass spectrometry experiments journal June 2009
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins journal December 2004
Antibody-free PRISM–SRM for multiplexed protein quantification: is this the new competition for immunoassays in bioanalysis? journal February 2013
Characterization of Purified c- Type Heme-Containing Peptides and Identification of c- Type Heme-Attachment Sites in Shewanella o neidenis Cytochromes Using Mass Spectrometry journal June 2005
Mannose7 Glycan Isomer Characterization by IMS-MS/MS Analysis journal October 2012
The Roles of Multiple Proteomic Platforms in a Pipeline for New Diagnostics: Fig. 1. journal July 2005
Development of high throughput dispersive LC--ion mobility--TOFMS techniques for analysing the human plasma proteome journal January 2004
Gas-Phase Structure of the Histone Multimers Characterized by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation journal March 2013
Fully Automated Four-Column Capillary LC−MS System for Maximizing Throughput in Proteomic Analyses journal January 2008
Simultaneous fragmentation of multiple ions using IMS drift time dependent collision energies journal March 2008
Protein Complexes in the Gas Phase:  Technology for Structural Genomics and Proteomics journal August 2007
Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies journal October 2008
DNA Hairpin, Pseudoknot, and Cruciform Stability in a Solvent-Free Environment journal February 2009
Ion mobility-mass spectrometry analysis of isomeric carbohydrate precursor ions journal June 2009
Nanoflow LC/Ion Mobility/CID/TOF for Proteomics:  Analysis of a Human Urinary Proteome journal December 2003
ESI/Ion Trap/Ion Mobility/Time-of-Flight Mass Spectrometry for Rapid and Sensitive Analysis of Biomolecular Mixtures journal January 1999
Ion mobility-mass spectrometry of intact protein–ligand complexes for pharmaceutical drug discovery and development journal October 2013
Iron and Manganese in Anaerobic Respiration: Environmental Significance, Physiology, and Regulation journal October 1994
Development of a new ion mobility time-of-flight mass spectrometer journal February 2015
An LC-IMS-MS Platform Providing Increased Dynamic Range for High-Throughput Proteomic Studies journal February 2010
A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease journal June 2011
Repurposing Diflunisal for Familial Amyloid Polyneuropathy: A Randomized Clinical Trial journal December 2013
Increasing confidence of LC–MS identifications by utilizing ion mobility spectrometry journal November 2013
Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry journal April 2011
High-Sensitivity Ion Mobility Spectrometry/Mass Spectrometry Using Electrodynamic Ion Funnel Interfaces journal May 2005
An Automated and Multiplexed Method for High Throughput Peptide Immunoaffinity Enrichment and Multiple Reaction Monitoring Mass Spectrometry-based Quantification of Protein Biomarkers journal October 2009
Diastereomer Assignment of an Olefin-Linked Bis-paracyclophane by Ion Mobility Mass Spectrometry journal May 2004
Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease journal June 2009
Physiology and enzymology involved in denitrification by Shewanella putrefaciens. journal January 1997

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