Individual Ion Mass Spectrometry Enhances the Sensitivity and Sequence Coverage of Top-Down Mass Spectrometry
Open accessAbstract
Charge detection mass spectrometry (CDMS) is mainly utilized to determine the mass of intact molecules. Previous applications of CDMS have determined the mass-to-charge ratio and the charge of large polymers, DNA molecules, and native protein complexes, from which corresponding mass values could be assigned. Recent advances have demonstrated that CDMS using an Orbitrap mass analyzer yields the reliable assignment of integer charge states that enables individual ion mass spectrometry (I 2 MS) and spectral output directly into the mass domain. Here I 2 MS analysis was extended to isotopically resolved fragment ions from intact proteoforms for the first time. With a radically different bias for ion readout, I 2 MS identified low-abundance fragment ions containing many hundreds of residues that were undetectable by standard Orbitrap measurements, leading to a doubling in the sequence coverage of triosephosphate isomerase. Thus MS/MS with the detection of individual ions (MS/I 2 MS) provides a far greater ability to detect high mass fragment ions and exhibits strong complementarity to traditional spectral readout in this, its first application to top-down mass spectrometry.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Kafader et al. demonstrated increased sensitivity and sequence coverage when employing CDMS of intact protein analysis.
“Additionally, Kafader et. al demonstrated increase sensitivity and sequence coverage when employing CDMS of intact protein analysis [107].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [107]
CDMS is one of the most important recent developments for top-down proteomics.
“Arguably, one of the most important recent developments is charge detection mass spectrometry (CDMS) (also referred to as individual ion MS) for top-down proteomics [107–110].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [107]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Enzymatic assembly of DNA molecules up to several hundred kilobases
Gibson, D. G., Young, L., Chuang, R.-Y., Venter, J. C., Hutchison, C. A., & Smith, H. O. (2009) · Nature Methods · doi:10.1038/nmeth.1318 · Cited by 9,742 · see citing works
Progress in Top-Down Proteomics and the Analysis of Proteoforms
Toby, T. K., Fornelli, L., & Kelleher, N. L. (2016) · Annual Review of Analytical Chemistry · doi:10.1146/annurev-anchem-071015-041550 · Cited by 576 · see citing works
Self-citationTop Down proteomics: Facts and perspectives
Catherman, A. D., Skinner, O. S., & Kelleher, N. L. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.041 · Cited by 507 · see citing works
Self-citationSenko, M. W., Beu, S. C., & McLaffertycor, F. W. (1995) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(95)00017-8 · Cited by 451 · see citing works
Self-citationMass Spectrometry: Bottom-Up or Top-Down?
Chait, B. T. (2006) · Science · doi:10.1126/science.1133987 · Cited by 442 · see citing works
Extending Top-Down Mass Spectrometry to Proteins with Masses Greater Than 200 Kilodaltons
Han, X., Jin, M., Breuker, K., & McLafferty, F. W. (2006) · Science · doi:10.1126/science.1128868 · Cited by 328 · see citing works
ProSight Lite: Graphical software to analyze top‐down mass spectrometry data
Fellers, R. T., Greer, J. B., Early, B. P., Yu, X., LeDuc, R. D., Kelleher, N. L., & Thomas, P. M. (2015) · PROTEOMICS · doi:10.1002/pmic.201400313 · Cited by 247 · see citing works
Self-citationMartin, R. W., Soye, B. J. D., Kwon, Y., Kay, J., Davis, R. G., Thomas, P. M., Majewska, N. I., Chen, C. X., Marcum, R. D., Weiss, M. G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03469-5 · Cited by 215 · see citing works
Self-citationBenner, W. H. (1997) · Analytical Chemistry · doi:10.1021/ac970163e · Cited by 202 · see citing works
Kafader, J. O., Melani, R. D., Durbin, K. R., Ikwuagwu, B., Early, B. P., Fellers, R. T., Beu, S. C., Zabrouskov, V., Makarov, A. A., Maze, J. T., et al. (2020) · Nature Methods · doi:10.1038/s41592-020-0764-5 · Cited by 197 · see citing works
Self-citationWörner, T. P., Snijder, J., Bennett, A., Agbandje-McKenna, M., Makarov, A. A., & Heck, A. J. R. (2020) · Nature Methods · doi:10.1038/s41592-020-0770-7 · Cited by 186 · see citing works
Belov, M. E., Damoc, E., Denisov, E., Compton, P. D., Horning, S., Makarov, A. A., & Kelleher, N. L. (2013) · Analytical Chemistry · doi:10.1021/ac4029328 · Cited by 175 · see citing works
Self-citationTop-down characterization of endogenous protein complexes with native proteomics
Skinner, O. S., Haverland, N. A., Fornelli, L., Melani, R. D., Do Vale, L. H. F., Seckler, H. S., Doubleday, P. F., Schachner, L. F., Srzentić, K., Kelleher, N. L., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2515 · Cited by 155 · see citing works
Self-citationCharge detection mass spectrometry: weighing heavier things
Keifer, D. Z., Pierson, E. E., & Jarrold, M. F. (2017) · The Analyst · doi:10.1039/c7an00277g · Cited by 130 · see citing works
Rapid Calculation of Isotope Distributions
Rockwood, A. L., Orden, S. L. V., & Smith, R. (1995) · Analytical Chemistry · doi:10.1021/ac00111a031 · Cited by 130 · see citing works
Cover Picture: Proteomics 7'15
Fellers, R. T., Greer, J. B., Early, B. P., Yu, X., LeDuc, R. D., Kelleher, N. L., & Thomas, P. M. (2015) · PROTEOMICS · doi:10.1002/pmic.201570050 · Cited by 122 · see citing works
Self-citationUltrahigh-Speed Calculation of Isotope Distributions
Rockwood, A. L., & Orden, S. L. V. (1996) · Analytical Chemistry · doi:10.1021/ac951158i · Cited by 122 · see citing works
Charge Detection Mass Spectrometry with Almost Perfect Charge Accuracy
Keifer, D. Z., Shinholt, D. L., & Jarrold, M. F. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02324 · Cited by 113 · see citing works
Measurement of Individual Ions Sharply Increases the Resolution of Orbitrap Mass Spectra of Proteins
Kafader, J. O., Melani, R. D., Senko, M. W., Makarov, A. A., Kelleher, N. L., & Compton, P. D. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b04519 · Cited by 87 · see citing works
Self-citationSTORI Plots Enable Accurate Tracking of Individual Ion Signals
Kafader, J. O., Beu, S. C., Early, B. P., Melani, R. D., Durbin, K. R., Zabrouskov, V., Makarov, A. A., Maze, J. T., Shinholt, D. L., Yip, P. F., et al. (2019) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-019-02309-0 · Cited by 85 · see citing works
Self-citationMass, mobility and MS n measurements of single ions using charge detection mass spectrometry
Elliott, A. G., Harper, C. C., Lin, H.-W., & Williams, E. R. (2017) · The Analyst · doi:10.1039/c7an00618g · Cited by 69 · see citing works
An informatic framework for decoding protein complexes by top-down mass spectrometry
Skinner, O. S., Havugimana, P. C., Haverland, N. A., Fornelli, L., Early, B. P., Greer, J. B., Fellers, R. T., Durbin, K. R., do Vale, L. H. F., Melani, R. D., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3731 · Cited by 64 · see citing works
Self-citationHaverland, N. A., Skinner, O. S., Fellers, R. T., Tariq, A., Early, B. P., LeDuc, R. D., Fornelli, L., Compton, P. D., & Kelleher, N. L. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-017-1635-x · Cited by 63 · see citing works
Self-citationMeasurement of the accurate mass of a 50 MDa infectious virus
Keifer, D. Z., Motwani, T., Teschke, C. M., & Jarrold, M. F. (2016) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.7673 · Cited by 55 · see citing works
Standard Proteoforms and Their Complexes for Native Mass Spectrometry
Schachner, L. F., Ives, A. N., McGee, J. P., Melani, R. D., Kafader, J. O., Compton, P. D., Patrie, S. M., & Kelleher, N. L. (2019) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-019-02191-w · Cited by 48 · see citing works
Self-citationMultiplexed Single Ion Mass Spectrometry Improves Measurement of Proteoforms and Their ComplexesPreprint
Kafader, J. O., Melani, R. D., Durbin, K. R., Ikwuagwu, B. C., Early, B. P., Fellers, R. T., Beu, S. C., Zabrouskov, V., Makarov, A., Maze, J. T., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/715425 · Cited by 2 · see citing works
Self-citationWörner, T. P., Snijder, J., Bennett, A. D., Agbandje‐McKenna, M., Makarov, A., & Heck, A. J. R. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/717413 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [14]Kafader JO STORI Plots Enable Accurate Tracking of Individual Ion Signals. Journal of The American Society for Mass Spectrometry (2019). PMC6852666 31512223
Cited by
Sorted by citations
Top-down proteomics: challenges, innovations, and applications in basic and clinical research
Brown, K. A., Melby, J. A., Roberts, D. S., & Ge, Y. (2020) · Expert Review of Proteomics · doi:10.1080/14789450.2020.1855982 · Cited by 152 · see citing works
STORI Plots Enable Accurate Tracking of Individual Ion Signals
Kafader, J. O., Beu, S. C., Early, B. P., Melani, R. D., Durbin, K. R., Zabrouskov, V., Makarov, A. A., Maze, J. T., Shinholt, D. L., Yip, P. F., et al. (2019) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-019-02309-0 · Cited by 85 · see citing works
Self-citation
- Authors
- Kafader, J. O., Durbin, K. R., Melani, R. D., Des Soye, B. J., Schachner, L. F., Senko, M. W., Compton, P. D., & Kelleher, N. L.
- Affiliations
- Northwestern University (US)
- Departments of Chemistry and Molecular Biosciences, the Chemistry of Life Processes Institute, and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois 60208, United States
- Thermo Fisher Scientific (United States) (US)
- Corresponding author
- Kelleher, Neil L.
- ORCID
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-02-07
- Volume
- 19
- Issue
- 3
- Pages
- 1346-1350
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- PMC
- PMC7060802
- OpenAlex
- W3005216464
- Cited by
- 76
- References
- 27
- Citations by year
- 2026: 21 · 2025: 12 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 2 · 2019: 1
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute (Gilliam Fellow)
- Thermo Fisher Scientific (Intensifying Innovation Program)
- National Institute of General Medical Sciences (P41 GM108569)
- American Society of Mass Spectrometry (Post-doctoral Career Development Award)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- top-down mass spectrometry, charge detection mass spectrometry, proteoforms, sequencing depth, triosephosphate isomerase, tandem mass spectrometry
- MeSH terms
- Ions, Proteomics, Tandem Mass Spectrometry
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
