The Value of Activated Ion Electron Transfer Dissociation for High-Throughput Top-Down Characterization of Intact Proteins
Open accessAbstract
High-throughput top-down proteomic experiments directly identify proteoforms in complex mixtures, making high quality tandem mass spectra necessary to deeply characterize proteins with many sources of variation. Collision-based dissociation methods offer expedient data acquisition but often fail to extensively fragment proteoforms for thorough analysis. Electron-driven dissociation methods are a popular alternative approach, especially for precursor ions with high charge density. Combining infrared photoactivation concurrent with electron transfer dissociation (ETD) reactions, i.e., activated ion ETD (AI-ETD), can significantly improve ETD characterization of intact proteins, but benefits of AI-ETD have yet to be quantified in high-throughput top-down proteomics. Here, we report the first application of AI-ETD to LC-MS/MS characterization of intact proteins (<20 kDa), highlighting improved proteoform identification the method offers over higher energy-collisional dissociation (HCD), standard ETD, and ETD followed by supplemental HCD activation (EThcD). We identified 935 proteoforms from 295 proteins from human colorectal cancer cell line HCT116 using AI-ETD compared to 1014 proteoforms, 915 proteoforms, and 871 proteoforms with HCD, ETD, and EThcD, respectively. Importantly, AI-ETD outperformed each of the three other methods in MS/MS success rates and spectral quality metrics (e.g., sequence coverage achieved and proteoform characterization scores). In all, this four-method analysis offers the most extensive comparisons to date and demonstrates that AI-ETD both increases identifications over other ETD methods and improves proteoform characterization via higher sequence coverage, positioning it as a premier method for high-throughput top-down proteomics.
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In a cited study, AI-ETD identified 935 proteoforms, while HCD, ETD, and EThcD identified 1014, 915, and 817 proteoforms, respectively.
“For example, Riley et al. demonstrated AI-ETD could identify 935 proteoforms while HCD, ETD, and EThcD identified 1014 proteoforms, 915, and 817, respectively [121].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [121]
AI-ETD generally performed better than HCD, ETD, and EThcD in sequence coverage and proteoform characterization scores.
“Importantly, AI-ETD generally outperformed HCD, ETD, and EThCD in terms of sequence coverage and proteoform characterization scores.”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [121]
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Cites
Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels.
Shevchenko, A., Wilm, M., Vorm, O., & Mann, M. F. (1996) · Analytical Chemistry · doi:10.1021/ac950914h · Cited by 9,047 · see citing works
Wessel, D., & Flügge, U. (1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90782-6 · Cited by 3,997 · see citing works
Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry
Syka, J. E. P., Coon, J. J., Schroeder, M. J., Shabanowitz, J., & Hunt, D. F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402700101 · Cited by 2,370 · see citing works
Self-citationMass-spectrometric exploration of proteome structure and function
Aebersold, R., & Mann, M. (2016) · Nature · doi:10.1038/nature19949 · Cited by 2,334 · see citing works
Electron Capture Dissociation of Multiply Charged Protein Cations. A Nonergodic Process
Zubarev, R. A., Kelleher, N. L., & McLafferty, F. W. (1998) · Journal of the American Chemical Society · doi:10.1021/ja973478k · Cited by 1,881 · see citing works
Self-citationProteoform: a single term describing protein complexity
The Consortium for Top Down Proteomics, Smith, L. M., & Kelleher, N. L. (2013) · Nature Methods · doi:10.1038/nmeth.2369 · Cited by 1,528 · see citing works
Self-citationProtein Analysis by Shotgun/Bottom-up Proteomics
Zhang, Y., Fonslow, B. R., Shan, B., Baek, M.-C., & Yates, J. R. (2013) · Chemical Reviews · doi:10.1021/cr3003533 · Cited by 1,491 · see citing works
How many human proteoforms are there?
Aebersold, R., Agar, J. N., Amster, I. J., Baker, M. S., Bertozzi, C. R., Boja, E. S., Costello, C. E., Cravatt, B. F., Fenselau, C., Garcia, B. A., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2576 · Cited by 907 · see citing works
Self-citationMapping intact protein isoforms in discovery mode using top-down proteomics
Tran, J. C., Zamdborg, L., Ahlf, D. R., Lee, J. E., Catherman, A. D., Durbin, K. R., Tipton, J. D., Vellaichamy, A., Kellie, J. F., Li, M., et al. (2011) · Nature · doi:10.1038/nature10575 · Cited by 665 · see citing works
Self-citationProgress 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-citationHebert, A. S., Richards, A. L., Bailey, D. J., Ulbrich, A., Coughlin, E. E., Westphall, M. S., & Coon, J. J. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.034769 · Cited by 528 · 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-citationDecoding protein modifications using top-down mass spectrometry
Siuti, N., & Kelleher, N. L. (2007) · Nature Methods · doi:10.1038/nmeth1097 · Cited by 503 · see citing works
Self-citationAn Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes
Bekker‐Jensen, D. B., Kelstrup, C. D., Batth, T. S., Buch-Larsen, S. C., Haldrup, C., Bramsen, J. B., Sørensen, K. D., Høyer, S., Orntoft, T. F., Andersen, C. L., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2017.05.009 · Cited by 467 · see citing works
Performance Characteristics of Electron Transfer Dissociation Mass Spectrometry
Good, D. M., Wirtala, M., McAlister, G. C., & Coon, J. J. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700073-mcp200 · Cited by 397 · see citing works
Self-citationProtein identification using sequential ion/ion reactions and tandem mass spectrometry
Coon, J. J., Ueberheide, B., Syka, J. E. P., Dryhurst, D. D., Ausio, J., Shabanowitz, J., & Hunt, D. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503189102 · Cited by 373 · see citing works
Self-citationComplete Protein Characterization Using Top-Down Mass Spectrometry and Ultraviolet Photodissociation
Shaw, J. B., Li, W., Holden, D. D., Zhang, Y., Griep-Raming, J., Fellers, R. T., Early, B. P., Thomas, P. M., Kelleher, N. L., & Brodbelt, J. S. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4029654 · Cited by 371 · see citing works
Self-citationSwaney, D. L., McAlister, G. C., Wirtala, M., Schwartz, J. C., Syka, J. E. P., & Coon, J. J. (2006) · Analytical Chemistry · doi:10.1021/ac061457f · Cited by 364 · see citing works
Self-citationGe, Y., Lawhorn, B. G., ElNaggar, M., Strauss, E., Park, J.-H., Begley, T. P., & McLafferty, F. W. (2002) · Journal of the American Chemical Society · doi:10.1021/ja011335z · Cited by 356 · see citing works
Activated Ion Electron Capture Dissociation for Mass Spectral Sequencing of Larger (42 kDa) Proteins
Horn, D. M., Ge, Y. P., & McLafferty, F. W. (2000) · Analytical Chemistry · doi:10.1021/ac000494i · Cited by 333 · see citing works
Proteoforms as the next proteomics currency
Smith, L. M., & Kelleher, N. L. (2018) · Science · doi:10.1126/science.aat1884 · Cited by 322 · see citing works
Self-citationScheltema, R. A., Hauschild, J.-P., Lange, O., Hornburg, D., Denisov, E. V., Damoc, E., Kuehn, A., Makarov, A., & Mann, M. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.043489 · Cited by 321 · see citing works
Frese, C. K., Altelaar, M. A. F., van den Toorn, H., Nolting, D., Griep‐Raming, J., Heck, A. J. R., & Mohammed, S. (2012) · Analytical Chemistry · doi:10.1021/ac3025366 · Cited by 300 · see citing works
Sze, S. K., Ge, Y., Oh, H. B., & McLafferty, F. W. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251691898 · Cited by 250 · see citing works
Håkansson, K., Chalmers, M. J., Quinn, J. P., McFarland, M. A., Hendrickson, C. L., & Marshall, A. G. (2003) · Analytical Chemistry · doi:10.1021/ac030015q · Cited by 246 · see citing works
Ion Activation Methods for Peptides and Proteins
Brodbelt, J. S. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04563 · Cited by 245 · see citing works
Senko, M. W., Remes, P. M., Canterbury, J. D., Mathur, R., Song, Q., Eliuk, S. M., Mullen, C., Earley, L., Hardman, M., Blethrow, J. D., et al. (2013) · Analytical Chemistry · doi:10.1021/ac403115c · Cited by 238 · see citing works
Huang, Y., Triscari, J. M., Tseng, G. C., Paša‐Tolić, L., Lipton, M. S. W., Smith, R. D., & Wysocki, V. H. (2005) · Analytical Chemistry · doi:10.1021/ac0480949 · Cited by 227 · see citing works
Top-Down Proteomics: Ready for Prime Time?
Chen, B., Brown, K. A., Lin, Z., & Ge, Y. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.7b04747 · Cited by 210 · see citing works
Informatics and multiplexing of intact protein identification in bacteria and the archaea
Meng, F., Cargile, B. J., Miller, L. M., Forbes, A. J., Johnson, J. R., & Kelleher, N. L. (2001) · Nature Biotechnology · doi:10.1038/nbt1001-952 · Cited by 210 · see citing works
Self-citationThe Role of Electron Transfer Dissociation in Modern Proteomics
Riley, N. M., & Coon, J. J. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b04810 · Cited by 180 · see citing works
Self-citationKelstrup, C. D., Jersie-Christensen, R., Batth, T. S., Arrey, T. N., Kuehn, A., Kellmann, M., & Olsen, J. V. (2014) · Journal of Proteome Research · doi:10.1021/pr500985w · Cited by 170 · see citing works
Dorrestein, P. C., Bumpus, S. B., Calderone, C. T., Garneau‐Tsodikova, S., Aron, Z. D., Straight, P. D., Kolter, R., Walsh, C. T., & Kelleher, N. L. (2006) · Biochemistry · doi:10.1021/bi061169d · Cited by 165 · see citing works
Self-citationCatherman, A. D., Durbin, K. R., Ahlf, D. R., Early, B. P., Fellers, R. T., Tran, J. C., Thomas, P. M., & Kelleher, N. L. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.030114 · Cited by 157 · see citing works
Self-citationElectron capture/transfer versus collisionally activated/induced dissociations: Solo or duet?
Zubarev, R. A., Zubarev, A. R., & Savitski, M. M. (2008) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2008.03.007 · Cited by 151 · see citing works
Collisions or Electrons? Protein Sequence Analysis in the 21st Century
Coon, J. J. (2009) · Analytical Chemistry · doi:10.1021/ac802330b · Cited by 149 · see citing works
Self-citationRapid and Deep Human Proteome Analysis by Single-dimension Shotgun Proteomics
Pirmoradian, M., Budamgunta, H., Chingin, K., Zhang, B., Astorga-Wells, J., & Zubarev, R. A. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o113.028787 · Cited by 144 · see citing works
Tsybin, Y. O., Witt, M., Baykut, G., Kjeldsen, F., & Håkansson, P. (2003) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1118 · Cited by 141 · see citing works
Cai, W., Tucholski, T., Chen, B., Alpert, A. J., McIlwain, S., Kohmoto, T., Jin, S., & Ge, Y. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00380 · Cited by 135 · see citing works
Pitteri, S. J., Chrisman, P. A., & McLuckey, S. A. (2005) · Analytical Chemistry · doi:10.1021/ac050666h · Cited by 122 · see citing works
Brunner, A. M., Lössl, P., Liu, F., Huguet, R., Mullen, C., Yamashita, M., Zabrouskov, V., Makarov, A., Altelaar, M. A. F., & Heck, A. J. R. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b00162 · Cited by 121 · see citing works
One-hour proteome analysis in yeast
Richards, A., Hebert, A. S., Ulbrich, A., Bailey, D. J., Coughlin, E. E., Westphall, M. S., & Coon, J. J. (2015) · Nature Protocols · doi:10.1038/nprot.2015.040 · Cited by 116 · see citing works
Self-citationQuantitation and Identification of Thousands of Human Proteoforms below 30 kDa
Durbin, K. R., Fornelli, L., Fellers, R. T., Doubleday, P. F., Narita, M., & Kelleher, N. L. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00997 · Cited by 111 · see citing works
Self-citationFeng, D., Witkowski, A., & Smith, S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m806991200 · Cited by 109 · see citing works
Ledvina, A. R., McAlister, G. C., Gardner, M. W., Smith, S. I., Madsen, J. A., Schwartz, J. C., Stafford, G. C., Syka, J. E. P., Brodbelt, J. S., & Coon, J. J. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200903557 · Cited by 101 · see citing works
Self-citationCleland, T. P., DeHart, C. J., Fellers, R. T., VanNispen, A. J., Greer, J. B., LeDuc, R. D., Parker, W. R., Thomas, P. M., Kelleher, N. L., & Brodbelt, J. S. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00043 · Cited by 96 · see citing works
Self-citationAnderson, L. C., DeHart, C. J., Kaiser, N. K., Fellers, R. T., Smith, D. F., Greer, J. B., LeDuc, R. D., Blakney, G. T., Thomas, P. M., Kelleher, N. L., et al. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00696 · Cited by 94 · see citing works
Self-citationThe Mechanism Behind Top-Down UVPD Experiments: Making Sense of Apparent Contradictions
Julian, R. R. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-017-1721-0 · Cited by 94 · see citing works
Ultraviolet Photodissociation for Characterization of Whole Proteins on a Chromatographic Time Scale
Cannon, J. R., Cammarata, M. B., Robotham, S. A., Cotham, V. C., Shaw, J., Fellers, R. T., Early, B. P., Thomas, P. M., Kelleher, N. L., & Brodbelt, J. S. (2014) · Analytical Chemistry · doi:10.1021/ac403859a · Cited by 92 · see citing works
Self-citationEvaluation of the Compact High-Field Orbitrap for Top-Down Proteomics of Human Cells
Ahlf, D. R., Compton, P. D., Tran, J. C., Early, B. P., Thomas, P. M., & Kelleher, N. L. (2012) · Journal of Proteome Research · doi:10.1021/pr3004216 · Cited by 89 · see citing works
Self-citationFornelli, L., Durbin, K. R., Fellers, R. T., Early, B. P., Greer, J. B., LeDuc, R. D., Compton, P. D., & Kelleher, N. L. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00698 · Cited by 88 · see citing works
Self-citationLermyte, F., Konijnenberg, A., Williams, J. P., Brown, J. M., Valkenborg, D., & Sobott, F. (2014) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-013-0798-3 · Cited by 87 · see citing works
LeDuc, R. D., Fellers, R. T., Early, B. P., Greer, J. B., Thomas, P. M., & Kelleher, N. L. (2014) · Journal of Proteome Research · doi:10.1021/pr401277r · Cited by 85 · see citing works
Self-citationActivated Ion Electron Transfer Dissociation for Improved Fragmentation of Intact Proteins
Riley, N. M., Westphall, M. S., & Coon, J. J. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b00881 · Cited by 80 · see citing works
Self-citationActivated Ion-Electron Transfer Dissociation Enables Comprehensive Top-Down Protein Fragmentation
Riley, N. M., Westphall, M. S., & Coon, J. J. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00249 · Cited by 79 · see citing works
Self-citationTop Down Proteomics of Human Membrane Proteins from Enriched Mitochondrial Fractions
Catherman, A. D., Li, M., Tran, J. C., Durbin, K. R., Compton, P. D., Early, B. P., Thomas, P. M., & Kelleher, N. L. (2013) · Analytical Chemistry · doi:10.1021/ac3031527 · Cited by 76 · see citing works
Self-citationSze, S. K., Ge, Y., Oh, H. B., & McLafferty, F. W. (2003) · Analytical Chemistry · doi:10.1021/ac020446t · Cited by 72 · see citing works
Ledvina, A. R., Beauchene, N. A., McAlister, G. C., Syka, J. E. P., Schwartz, J. C., Griep‐Raming, J., Westphall, M. S., & Coon, J. J. (2010) · Analytical Chemistry · doi:10.1021/ac1020358 · Cited by 71 · see citing works
Self-citationTsybin, Y. O., He, H. Q., Emmett, M. R., Hendrickson, C. L., & Marshall, A. G. (2007) · Analytical Chemistry · doi:10.1021/ac071165u · Cited by 68 · see citing works
Improved Precursor Characterization for Data-Dependent Mass Spectrometry
Hebert, A. S., Thöing, C., Riley, N. M., Kwiecien, N. W., Shiskova, E., Huguet, R., Cardasis, H. L., Kuehn, A., Eliuk, S., Zabrouskov, V., et al. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.7b04808 · Cited by 67 · see citing works
Self-citationZabrouskov, V., & Whitelegge, J. P. (2007) · Journal of Proteome Research · doi:10.1021/pr0607031 · Cited by 66 · see citing works
Lermyte, F., & Sobott, F. (2015) · PROTEOMICS · doi:10.1002/pmic.201400516 · Cited by 64 · see citing works
Haverland, 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-citationAnderson, L. C., Karch, K. R., Ugrin, S. A., Coradin, M., English, A. M., Sidoli, S., Shabanowitz, J., Garcia, B. A., & Hunt, D. F. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o115.053843 · Cited by 60 · see citing works
Xia, Y., Han, H., & McLuckey, S. A. (2008) · Analytical Chemistry · doi:10.1021/ac702188q · Cited by 59 · see citing works
Greer, S. M., & Brodbelt, J. S. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00801 · Cited by 58 · see citing works
Elurbe, D. M., & Huynen, M. A. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.03.027 · Cited by 57 · see citing works
Instant spectral assignment for advanced decision tree-driven mass spectrometry
Bailey, D. J., Rose, C. M., McAlister, G. C., Brumbaugh, J., Yu, P., Wenger, C. D., Westphall, M. S., Thomson, J. A., & Coon, J. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205292109 · Cited by 56 · see citing works
Self-citationZhao, Y., Riley, N. M., Sun, L., Hebert, A. S., Yan, X., Westphall, M. S., Rush, M. J. P., Zhu, G., Champion, M. M., Medie, F. M., et al. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b00883 · Cited by 55 · see citing works
Self-citationPhosphoproteomics with Activated Ion Electron Transfer Dissociation
Riley, N. M., Hebert, A. S., Dürnberger, G., Stanek, F., Mechtler, K., Westphall, M. S., & Coon, J. J. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00212 · Cited by 55 · see citing works
Self-citationSequencing Larger Intact Proteins (30–70 kDa) with Activated Ion Electron Transfer Dissociation
Riley, N., Westphall, M., & Coon, J. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-017-1808-7 · Cited by 55 · see citing works
Self-citationRiley, N. M., Westphall, M. S., Hebert, A. S., & Coon, J. J. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00213 · Cited by 52 · see citing works
Self-citationWeisbrod, C. R., Kaiser, N. K., Syka, J. E. P., Early, L., Mullen, C., Dunyach, J., English, A. M., Anderson, L. C., Blakney, G. T., Shabanowitz, J., et al. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-017-1702-3 · Cited by 49 · see citing works
Mikhailov, V. A., & Cooper, H. J. (2009) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2008.12.015 · Cited by 46 · see citing works
Cannon, J. R., Holden, D. D., & Brodbelt, J. S. (2014) · Analytical Chemistry · doi:10.1021/ac5036082 · Cited by 46 · see citing works
Proteomics Moves into the Fast Lane
Riley, N. M., Hebert, A. S., & Coon, J. J. (2016) · Cell Systems · doi:10.1016/j.cels.2016.03.002 · Cited by 44 · see citing works
Self-citationZhang, L., English, A. M., Bai, D. L., Ugrin, S. A., Shabanowitz, J., Ross, M. M., Hunt, D. F., & Wang, W. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o115.056721 · Cited by 42 · see citing works
Triepels, R. H., Smeitink, J. A. M., Loeffen, J. L. C., Smeets, R., Buskens, C. A. F., Trijbels, F. J. M., & van den Heuvel, L. P. (1999) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005402020569 · Cited by 42 · see citing works
Anderson, L. C., English, A. M., Wang, W.-H., Bai, D. L., Shabanowitz, J., & Hunt, D. F. (2015) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2014.06.023 · Cited by 37 · see citing works
Durbin, K. R., Fellers, R. T., Ntai, I., Kelleher, N. L., & Compton, P. D. (2014) · Analytical Chemistry · doi:10.1021/ac402904h · Cited by 35 · see citing works
Self-citationShaw, J., Robinson, E. W., & Paša‐Tolić, L. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b00148 · Cited by 34 · see citing works
Top-Down Mass Spectrometry: Proteomics to Proteoforms
Patrie, S. M. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-41448-5_8 · Cited by 34 · see citing works
Activated Ion ETD Performed in a Modified Collision Cell on a Hybrid QLT-Oribtrap Mass Spectrometer
Ledvina, A. R., Rose, C. M., McAlister, G. C., Syka, J. E. P., Westphall, M. S., Griep‐Raming, J., Schwartz, J. C., & Coon, J. J. (2013) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-013-0621-1 · Cited by 32 · see citing works
Self-citationFragmentation of Integral Membrane Proteins in the Gas Phase
Skinner, O. S., Catherman, A. D., Early, B. P., Thomas, P. M., Compton, P. D., & Kelleher, N. L. (2014) · Analytical Chemistry · doi:10.1021/ac500864w · Cited by 29 · see citing works
Self-citationTsybin, Y. O., Witt, M., Baykut, G., & Håkansson, P. (2004) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1525 · Cited by 29 · see citing works
Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin
Lermyte, F., Łącki, M. K., Valkenborg, D., Gambin, A., & Sobott, F. (2016) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-016-1444-7 · Cited by 28 · see citing works
Charge state dependent top‐down characterisation using electron transfer dissociation
Rožman, M., & Gaskell, S. J. (2011) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.5330 · Cited by 27 · see citing works
Beam‐type collisional activation of polypeptide cations that survive ion/ion electron transfer
Han, H., Xia, Y., & McLuckey, S. A. (2007) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.2994 · Cited by 22 · see citing works
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- [9]Bekker-Jensen DB Kelstrup CD Batth TS Larsen SC Haldrup C Bramsen JB Sorensen KD Hoyer S Orntoft TF Andersen CL Nielsen ML Olsen JV Cell Syst 2017 4 587 599 28601559 PMC5493283
- [78]Riley NM Westphall MS Coon JJ J Proteome Res 2017 16 2653 2659 28608681 PMC5555583
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- Authors
- Riley, N. M., Sikora, J. W., Seckler, H. S., Greer, J. B., Fellers, R. T., LeDuc, R. D., Westphall, M. S., Thomas, P. M., Kelleher, N. L., & Coon, J. J.
- Affiliations
- University of Wisconsin–Madison (US)
- Northwestern University (US)
- Morgridge Institute for Research (US)
- Corresponding author
- Coon, Joshua J.
- ORCID
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-06-20
- Volume
- 90
- Issue
- 14
- Pages
- 8553-8560
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC6050102
- OpenAlex
- W2808811369
- Cited by
- 43
- References
- 88
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 10 · 2018: 2
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (F99CA212454)
- Thermo Fisher Scientific
- National Institute of General Medical Sciences (P41GM108569, P41GM108538)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- top-down proteomics, proteoform identification, electron transfer dissociation, tandem mass spectrometry, high-throughput proteomics, HCT116 cells, sequencing depth
- MeSH terms
- Amino Acid Sequence, Chromatography, Liquid, Electron Transport, Electrons, Humans, Protein Processing, Post-Translational, Proteins, Colorectal Neoplasms, Proteomics, Cell Line, Tumor, Tandem Mass Spectrometry, Photochemical Processes, High-Throughput Screening Assays
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