Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

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

Abstract

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.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [1]
+ Show Author Affiliations
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Boston Univ. of Medicine, MA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1212228
Report Number(s):
PNNL-SA-107785
Journal ID: ISSN 1615-9853; 48135; 48203; 400412000
Grant/Contract Number:  
AC05-76RL01830; R01ES022190; P41 GM103493; P41 GM104603
Resource Type:
Accepted Manuscript
Journal Name:
Proteomics
Additional Journal Information:
Journal Volume: 15; Journal Issue: 16; Journal ID: ISSN 1615-9853
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Ion mobility separations; Ion mobility spectrometry; Mass spectrometry; Proteomics; Environmental Molecular Sciences Laboratory

Citation Formats

Baker, Erin Shammel, Burnum-Johnson, Kristin E., Ibrahim, Yehia M., Orton, Daniel J., Monroe, Matthew E., Kelly, Ryan T., Moore, Ronald J., Zhang, Xing, Theberge, Roger, Costello, Catherine E., and Smith, Richard D. Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations. United States: N. p., 2015. Web. doi:10.1002/pmic.201500048.
Copy to clipboard
Baker, Erin Shammel, Burnum-Johnson, Kristin E., Ibrahim, Yehia M., Orton, Daniel J., Monroe, Matthew E., Kelly, Ryan T., Moore, Ronald J., Zhang, Xing, Theberge, Roger, Costello, Catherine E., & Smith, Richard D. Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations. United States. https://doi.org/10.1002/pmic.201500048
Copy to clipboard
Baker, Erin Shammel, Burnum-Johnson, Kristin E., Ibrahim, Yehia M., Orton, Daniel J., Monroe, Matthew E., Kelly, Ryan T., Moore, Ronald J., Zhang, Xing, Theberge, Roger, Costello, Catherine E., and Smith, Richard D. Fri . "Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations". United States. https://doi.org/10.1002/pmic.201500048. https://www.osti.gov/servlets/purl/1212228.
Copy to clipboard
@article{osti_1212228,
title = {Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations},
author = {Baker, Erin Shammel and Burnum-Johnson, Kristin E. and Ibrahim, Yehia M. and Orton, Daniel J. and Monroe, Matthew E. and Kelly, Ryan T. and Moore, Ronald J. and Zhang, Xing and Theberge, Roger and Costello, Catherine E. and Smith, Richard D.},
abstractNote = {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.},
doi = {10.1002/pmic.201500048},
journal = {Proteomics},
number = 16,
volume = 15,
place = {United States},
year = {Fri Jul 03 00:00:00 EDT 2015},
month = {Fri Jul 03 00:00:00 EDT 2015}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1002/pmic.201500048
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 46 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements
journal, May 2014

  • Prost, Spencer A.; Crowell, Kevin L.; Baker, Erin S.
  • Journal of The American Society for Mass Spectrometry, Vol. 25, Issue 12
  • DOI: 10.1007/s13361-014-0895-y

Ion mobility spectrometry—mass spectrometry performance using electrodynamic ion funnels and elevated drift gas pressures
journal, July 2007

  • Baker, Erin Shammel; Clowers, Brian H.; Li, Fumin
  • Journal of the American Society for Mass Spectrometry, Vol. 18, Issue 7, p. 1176-1187
  • DOI: 10.1016/j.jasms.2007.03.031

High-resolution separations and improved ion production and transmission in metabolomics
journal, March 2008

  • Metz, Thomas O.; Page, Jason S.; Baker, Erin S.
  • TrAC Trends in Analytical Chemistry, Vol. 27, Issue 3
  • DOI: 10.1016/j.trac.2007.11.003

Ion Mobility Measurements of Nondenatured 12–150 kDa Proteins and Protein Multimers by Tandem Differential Mobility Analysis–Mass Spectrometry (DMA-MS)
journal, January 2011

  • Hogan, Christopher J.; de la Mora, Juan Fernández
  • Journal of The American Society for Mass Spectrometry, Vol. 22, Issue 1
  • DOI: 10.1007/s13361-010-0014-7

Protein biomarker discovery and validation: the long and uncertain path to clinical utility
journal, August 2006

  • Rifai, Nader; Gillette, Michael A.; Carr, Steven A.
  • Nature Biotechnology, Vol. 24, Issue 8
  • DOI: 10.1038/nbt1235

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

  • Greene, Michael J.; Klimtchuk, Elena S.; Seldin, David C.
  • Biochemistry, Vol. 54, Issue 2
  • DOI: 10.1021/bi5011249

Combined Ion Mobility/Time-of-Flight Mass Spectrometry Study of Electrospray-Generated Ions
journal, October 1997

  • Guevremont, Roger; Siu, K. W. Michael; Wang, Jianyao
  • Analytical Chemistry, Vol. 69, Issue 19
  • DOI: 10.1021/ac970359e

A targeted proteomics–based pipeline for verification of biomarkers in plasma
journal, June 2011

  • Whiteaker, Jeffrey R.; Lin, Chenwei; Kennedy, Jacob
  • Nature Biotechnology, Vol. 29, Issue 7
  • DOI: 10.1038/nbt.1900

Toward Plasma Proteome Profiling with Ion Mobility-Mass Spectrometry
journal, November 2006

  • Valentine, Stephen J.; Plasencia, Manolo D.; Liu, Xiaoyun
  • Journal of Proteome Research, Vol. 5, Issue 11
  • DOI: 10.1021/pr060232i

Hadamard Transform Time-of-Flight Mass Spectrometry: More Signal, More of the Time
journal, January 2003

  • Zare, Richard N.; Fernández, Facundo M.; Kimmel, Joel R.
  • Angewandte Chemie International Edition, Vol. 42, Issue 1
  • DOI: 10.1002/anie.200390047

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

  • Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.
  • Molecular & Cellular Proteomics, Vol. 13, Issue 4, p. 1119-1127
  • DOI: 10.1074/mcp.M113.034595

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

  • Valentine, Stephen J.; Counterman, Anne E.; Hoaglund, Cherokee S.
  • Journal of the American Society for Mass Spectrometry, Vol. 9, Issue 11
  • DOI: 10.1016/S1044-0305(98)00101-9

Metrics for the Human Proteome Project 2013–2014 and Strategies for Finding Missing Proteins
journal, December 2013

  • Lane, Lydie; Bairoch, Amos; Beavis, Ronald C.
  • Journal of Proteome Research, Vol. 13, Issue 1
  • DOI: 10.1021/pr401144x

Dynamically Multiplexed Ion Mobility Time-of-Flight Mass Spectrometry
journal, August 2008

  • Belov, Mikhail E.; Clowers, Brian H.; Prior, David C.
  • Analytical Chemistry, Vol. 80, Issue 15
  • DOI: 10.1021/ac8003665

Utilizing Human Blood Plasma for Proteomic Biomarker Discovery †
journal, August 2005

  • Jacobs, Jon M.; Adkins, Joshua N.; Qian, Wei-Jun
  • Journal of Proteome Research, Vol. 4, Issue 4
  • DOI: 10.1021/pr0500657

Ion Mobility Derived Collision Cross Sections to Support Metabolomics Applications
journal, March 2014

  • Paglia, Giuseppe; Williams, Jonathan P.; Menikarachchi, Lochana
  • Analytical Chemistry, Vol. 86, Issue 8
  • DOI: 10.1021/ac500405x

NWChem: A comprehensive and scalable open-source solution for large scale molecular simulations
journal, September 2010

  • Valiev, M.; Bylaska, E. J.; Govind, N.
  • Computer Physics Communications, Vol. 181, Issue 9, p. 1477-1489
  • DOI: 10.1016/j.cpc.2010.04.018

Electrospray ionization with ambient pressure ion mobility separation and mass analysis by orthogonal time-of-flight mass spectrometry
journal, January 2001

  • Steiner, Wes E.; Clowers, Brian H.; Fuhrer, Katrin
  • Rapid Communications in Mass Spectrometry, Vol. 15, Issue 23
  • DOI: 10.1002/rcm.495

Phenotypic Mapping of Metabolic Profiles Using Self-Organizing Maps of High-Dimensional Mass Spectrometry Data
journal, June 2014

  • Goodwin, Cody R.; Sherrod, Stacy D.; Marasco, Christina C.
  • Analytical Chemistry, Vol. 86, Issue 13
  • DOI: 10.1021/ac5010794

Expression, purification, and in vitro cysteine-10 modification of native sequence recombinant human transthyretin
journal, June 2007

  • Kingsbury, Jonathan S.; Klimtchuk, Elena S.; Théberge, Roger
  • Protein Expression and Purification, Vol. 53, Issue 2
  • DOI: 10.1016/j.pep.2007.01.004

A novel approach to collision-induced dissociation (CID) for ion mobility-mass spectrometry experiments
journal, June 2009

  • Becker, Christopher; Fernandez-Lima, Francisco A.; Gillig, Kent J.
  • Journal of the American Society for Mass Spectrometry, Vol. 20, Issue 6
  • DOI: 10.1016/j.jasms.2008.11.026

NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins
journal, December 2004

  • Pruitt, K. D.
  • Nucleic Acids Research, Vol. 33, Issue Database issue
  • DOI: 10.1093/nar/gki025

Mannose7 Glycan Isomer Characterization by IMS-MS/MS Analysis
journal, October 2012

  • Zhu, Feifei; Lee, Sunyoung; Valentine, Stephen J.
  • Journal of The American Society for Mass Spectrometry, Vol. 23, Issue 12
  • DOI: 10.1007/s13361-012-0491-y

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

  • Liu, X.
  • Briefings in Functional Genomics and Proteomics, Vol. 3, Issue 2
  • DOI: 10.1093/bfgp/3.2.177

Gas-Phase Structure of the Histone Multimers Characterized by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation
journal, March 2013

  • Saikusa, Kazumi; Fuchigami, Sotaro; Takahashi, Kyohei
  • Analytical Chemistry, Vol. 85, Issue 8
  • DOI: 10.1021/ac400395j

Fully Automated Four-Column Capillary LC−MS System for Maximizing Throughput in Proteomic Analyses
journal, January 2008

  • Livesay, Eric A.; Tang, Keqi; Taylor, Beverley K.
  • Analytical Chemistry, Vol. 80, Issue 1
  • DOI: 10.1021/ac701727r

Simultaneous fragmentation of multiple ions using IMS drift time dependent collision energies
journal, March 2008

  • Baker, Erin Shammel; Tang, Keqi; Danielson, William F.
  • Journal of the American Society for Mass Spectrometry, Vol. 19, Issue 3
  • DOI: 10.1016/j.jasms.2007.11.018

Protein Complexes in the Gas Phase:  Technology for Structural Genomics and Proteomics
journal, August 2007

  • Benesch, Justin L. P.; Ruotolo, Brandon T.; Simmons, Douglas A.
  • Chemical Reviews, Vol. 107, Issue 8
  • DOI: 10.1021/cr068289b

Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies †
journal, October 2008

  • Johnson, Steven M.; Connelly, Stephen; Wilson, Ian A.
  • Journal of Medicinal Chemistry, Vol. 51, Issue 20
  • DOI: 10.1021/jm800435s

DNA Hairpin, Pseudoknot, and Cruciform Stability in a Solvent-Free Environment
journal, February 2009

  • Baker, Erin Shammel; Dupuis, Nicholas F.; Bowers, Michael T.
  • The Journal of Physical Chemistry B, Vol. 113, Issue 6
  • DOI: 10.1021/jp807529m

Ion mobility-mass spectrometry analysis of isomeric carbohydrate precursor ions
journal, June 2009

  • Zhu, Maolei; Bendiak, Brad; Clowers, Brian
  • Analytical and Bioanalytical Chemistry, Vol. 394, Issue 7
  • DOI: 10.1007/s00216-009-2865-y

Nanoflow LC/Ion Mobility/CID/TOF for Proteomics:  Analysis of a Human Urinary Proteome
journal, December 2003

  • Moon, Myeong Hee; Myung, Sunnie; Plasencia, Manolo
  • Journal of Proteome Research, Vol. 2, Issue 6
  • DOI: 10.1021/pr034018v

ESI/Ion Trap/Ion Mobility/Time-of-Flight Mass Spectrometry for Rapid and Sensitive Analysis of Biomolecular Mixtures
journal, January 1999

  • Henderson, Sheila C.; Valentine, Stephen J.; Counterman, Anne E.
  • Analytical Chemistry, Vol. 71, Issue 2
  • DOI: 10.1021/ac9809175

Ion mobility-mass spectrometry of intact protein–ligand complexes for pharmaceutical drug discovery and development
journal, October 2013

  • Niu, Shuai; Rabuck, Jessica N.; Ruotolo, Brandon T.
  • Current Opinion in Chemical Biology, Vol. 17, Issue 5
  • DOI: 10.1016/j.cbpa.2013.06.019

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

  • Ibrahim, Yehia M.; Baker, Erin S.; Danielson, William F.
  • International Journal of Mass Spectrometry, Vol. 377
  • DOI: 10.1016/j.ijms.2014.07.034

An LC-IMS-MS Platform Providing Increased Dynamic Range for High-Throughput Proteomic Studies
journal, February 2010

  • Baker, Erin Shammel; Livesay, Eric A.; Orton, Daniel J.
  • Journal of Proteome Research, Vol. 9, Issue 2
  • DOI: 10.1021/pr900888b

A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease
journal, June 2011

  • Addona, Terri A.; Shi, Xu; Keshishian, Hasmik
  • Nature Biotechnology, Vol. 29, Issue 7
  • DOI: 10.1038/nbt.1899

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

  • Crowell, Kevin L.; Baker, Erin S.; Payne, Samuel H.
  • International Journal of Mass Spectrometry, Vol. 354-355
  • DOI: 10.1016/j.ijms.2013.06.028

Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry
journal, April 2011

  • Shvartsburg, Alexandre A.; Isaac, Giorgis; Leveque, Nathalie
  • Journal of The American Society for Mass Spectrometry, Vol. 22, Issue 7
  • DOI: 10.1007/s13361-011-0114-z

High-Sensitivity Ion Mobility Spectrometry/Mass Spectrometry Using Electrodynamic Ion Funnel Interfaces
journal, May 2005

  • Tang, Keqi; Shvartsburg, Alexandre A.; Lee, Hak-No
  • Analytical Chemistry, Vol. 77, Issue 10, p. 3330-3339
  • DOI: 10.1021/ac048315a

Diastereomer Assignment of an Olefin-Linked Bis-paracyclophane by Ion Mobility Mass Spectrometry
journal, May 2004

  • Baker, Erin Shammel; Hong, Janice W.; Gidden, Jennifer
  • Journal of the American Chemical Society, Vol. 126, Issue 20
  • DOI: 10.1021/ja039486k

Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease
journal, June 2009

  • Bernstein, Summer L.; Dupuis, Nicholas F.; Lazo, Noel D.
  • Nature Chemistry, Vol. 1, Issue 4
  • DOI: 10.1038/nchem.247

Physiology and enzymology involved in denitrification by Shewanella putrefaciens.
journal, January 1997

    Sort by:
    [ × clear filter / sort ]

    Works referencing / citing this record:

    Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease: Hepatology Communications
    journal, December 2018

    • Sharpton, Suzanne R.; Yong, Germaine J. M.; Terrault, Norah A.
    • Hepatology Communications, Vol. 3, Issue 1
    • DOI: 10.1002/hep4.1284

    The Skyline ecosystem: Informatics for quantitative mass spectrometry proteomics
    journal, July 2017

    • Pino, Lindsay K.; Searle, Brian C.; Bollinger, James G.
    • Mass Spectrometry Reviews
    • DOI: 10.1002/mas.21540

    Targeted and Untargeted Proteomics Approaches in Biomarker Development
    journal, January 2020

    • Sobsey, Constance A.; Ibrahim, Sahar; Richard, Vincent R.
    • PROTEOMICS, Vol. 20, Issue 9
    • DOI: 10.1002/pmic.201900029

    The past, present and future of microbiome analyses
    journal, September 2016

    • White, Richard Allen; Callister, Stephen J.; Moore, Ronald J.
    • Nature Protocols, Vol. 11, Issue 11
    • DOI: 10.1038/nprot.2016.148

    Profiling microbial lignocellulose degradation and utilization by emergent omics technologies
    journal, July 2016

    The fungal cultivar of leaf-cutter ants produces specific enzymes in response to different plant substrates
    journal, October 2016

    • Khadempour, Lily; Burnum-Johnson, Kristin E.; Baker, Erin S.
    • Molecular Ecology, Vol. 25, Issue 22
    • DOI: 10.1111/mec.13872

    Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease: Hepatology Communications
    journal, December 2018

    • Sharpton, Suzanne R.; Yong, Germaine J. M.; Terrault, Norah A.
    • Hepatology Communications, Vol. 3, Issue 1
    • DOI: 10.1002/hep4.1284
      Sort by:
      [ × clear filter / sort ]

      Similar Records in DOE PAGES and OSTI.GOV collections: