A Top-Down Proteomics Platform Coupling Serial Size Exclusion Chromatography and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
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Mass spectrometry (MS) based top-down proteomics provides rich information about proteoforms arising from combinatorial amino acid sequence variations and post-translational modifications (PTMs). Fourier transform ion cyclotron resonance (FT-ICR) MS affords ultrahigh resolving power and provides high-accuracy mass measurements, presenting a powerful tool for top-down MS characterization of proteoforms. However, the detection and characterization of large proteins from complex mixtures remain challenging due to the exponential decrease in S: N with increasing molecular weight (MW) and coeluting low-MW proteins; thus, size-based fractionation of complex protein mixtures prior to MS analysis is necessary. Here, we directly combine MS-compatible serial size exclusion chromatography (sSEC) fractionation with 12 T FT-ICR MS for targeted top-down characterization of proteins from complex mixtures extracted from human and swine heart tissue. Benefiting from the ultrahigh resolving power of FT-ICR, we isotopically resolved 31 distinct proteoforms (30-50 kDa) simultaneously in a single mass spectrum within a 100 m/ z window. Notably, within a 5 m/ z window, we obtained baseline isotopic resolution for 6 distinct large proteoforms (30-50 kDa). The ultrahigh resolving power of FT-ICR MS combined with sSEC fractionation enabled targeted top-down analysis of large proteoforms (>30 kDa) from the human heart proteome without extensive chromatographic separation or protein purification. Further separation of proteoforms inside the mass spectrometer (in-MS) allowed for isolation of individual proteoforms and targeted electron capture dissociation (ECD), yielding high sequence coverage. sSEC/FT-ICR ECD facilitated the identification and sequence characterization of important metabolic enzymes. This platform, which facilitates deep interrogation of proteoform primary structure, is highly tunable, allows for adjustment of MS and MS/MS parameters in real time, and can be utilized for a variety of complex protein mixtures.
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GPF can contribute to top-down proteomics in a similar manner to sophisticated multidimensional liquid phase separations.
“demonstrating that GPF can contribute to top-down proteomics in a similar manner to sophisticated multidimensional liquid phase separations.49-51”
From Proton Transfer Charge Reduction Enables High-Throughput Top-Down Analysis of Large Proteoforms (2019) · cites this paper as [49]
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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
Fourier transform ion cyclotron resonance mass spectrometry: A primer
Marshall, A. G., Hendrickson, C. L., & Jackson, G. S. (1998) · Mass Spectrometry Reviews · doi:10.1002/(sici)1098-2787(1998)17:1 · Cited by 1,992 · 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
Proteoform: 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
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
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
Zubarev, R. A., Kruger, N. A., Fridriksson, E. K., Lewis, M. A., Horn, D. M., Carpenter, B. K., & McLafferty, F. W. (1999) · Journal of the American Chemical Society · doi:10.1021/ja981948k · Cited by 557 · see citing works
Decoding 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
Space charge effects in Fourier transform mass spectrometry. II. Mass calibration
Ledford, E. B., Rempel, D. L., & Gross, M. L. (1984) · Analytical Chemistry · doi:10.1021/ac00278a027 · Cited by 469 · see citing works
Senko, 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
Myoglobin: an essential hemoprotein in striated muscle
Ordway, G. A., & Garry, D. J. (2004) · Journal of Experimental Biology · doi:10.1242/jeb.01172 · Cited by 445 · see citing works
Ge, 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
Self-citationExtending 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
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
Photodissociation mass spectrometry: new tools for characterization of biological molecules
Brodbelt, J. S. (2014) · Chemical Society Reviews · doi:10.1039/c3cs60444f · Cited by 322 · see citing works
Kou, Q., Xun, L., & Liu, X. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw398 · Cited by 276 · see citing works
Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man
Kleine, A. H., Glatz, J. F. C., van Nieuwenhoven, F. A., & Vusse, G. J. (1992) · Molecular and Cellular Biochemistry · doi:10.1007/bf01270583 · Cited by 265 · 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
Self-citationLi, H., Nguyen, H. H., Ogorzalek Loo, R. R., Campuzano, I. D. G., & Loo, J. A. (2018) · Nature Chemistry · doi:10.1038/nchem.2908 · Cited by 249 · see citing works
On the Scalability and Requirements of Whole Protein Mass Spectrometry
Compton, P. D., Zamdborg, L., Thomas, P. M., & Kelleher, N. L. (2011) · Analytical Chemistry · doi:10.1021/ac2010795 · Cited by 243 · see citing works
Zhurov, K. O., Fornelli, L., Wodrich, M. D., Laskay, Ü. A., & Tsybin, Y. O. (2013) · Chemical Society Reviews · doi:10.1039/c3cs35477f · Cited by 226 · 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
Self-citationSerum and urinary human heart fatty acid-binding protein in acute myocardial infarction
Tanaka, T., Hirota, Y., Sohmiya, K.-I., Nishimura, S., & Kawamura, K. (1991) · Clinical Biochemistry · doi:10.1016/0009-9120(91)90571-u · Cited by 208 · see citing works
Tran, J. C., & Doucette, A. A. (2008) · Analytical Chemistry · doi:10.1021/ac702197w · Cited by 206 · see citing works
Zhang, J., Guy, M. J., Norman, H. S., Chen, Y.-C., Xu, Q., Dong, X., Guner, H., Wang, S., Kohmoto, T., Young, K. H., et al. (2011) · Journal of Proteome Research · doi:10.1021/pr200258m · Cited by 194 · see citing works
Self-citationChamot-Rooke, J., Mikaty, G., Malosse, C., Soyer, M., Dumont, A., Gault, J., Imhaus, A.-F., Martin, P., Trellet, M., Clary, G., et al. (2011) · Science · doi:10.1126/science.1200729 · Cited by 180 · see citing works
Ansong, C., Wu, S., Meng, D., Liu, X., Brewer, H. M., Deatherage Kaiser, B. L., Nakayasu, E. S., Cort, J. R., Pevzner, P., Smith, R. D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221210110 · Cited by 157 · see citing works
Ge, Y., Rybakova, I. N., Xu, Q., & Moss, R. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813369106 · Cited by 154 · see citing works
Self-citationCai, 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
Self-citationMASH Suite Pro: A Comprehensive Software Tool for Top-Down Proteomics
Cai, W., Guner, H., Gregorich, Z. R., Chen, A. J., Ayaz-Guner, S., Peng, Y., Valeja, S. G., Liu, X., & Ge, Y. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o115.054387 · Cited by 132 · see citing works
Self-citationMcCool, E. N., Lubeckyj, R. A., Shen, X., Chen, D., Kou, Q., Liu, X., & Sun, L. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b00693 · Cited by 117 · see citing works
Ntai, I., Fornelli, L., DeHart, C. J., Hutton, J. E., Doubleday, P. F., LeDuc, R. D., van Nispen, A. J., Fellers, R. T., Whiteley, G., Boja, E. S., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716122115 · Cited by 108 · see citing works
Peng, Y., Gregorich, Z. R., Valeja, S. G., Zhang, H., Cai, W., Chen, Y.-C., Guner, H., Chen, A. J., Schwahn, D. J., Hacker, T. A., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.040675 · Cited by 107 · see citing works
Self-citationAugmented Phosphorylation of Cardiac Troponin I in Hypertensive Heart Failure
Dong, X., Sumandea, C. A., Chen, Y.-C., Garcia-Cazarin, M. L., Zhang, J., Balke, C. W., Sumandea, M. P., & Ge, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.293258 · Cited by 99 · see citing works
Self-citationTop-down Proteomics: Technology Advancements and Applications to Heart Diseases
Cai, W., Tucholski, T. M., Gregorich, Z. R., & Ge, Y. (2016) · Expert Review of Proteomics · doi:10.1080/14789450.2016.1209414 · Cited by 99 · 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
Anderson, 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
Mass measurement errors caused by “local” frequency perturbations in FTICR mass spectrometry
Masselon, C., Tolmachev, A. V., Anderson, G., Harkewicz, R., & Smith, R. D. (2002) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(01)00333-6 · Cited by 82 · see citing works
Activated 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
Ge, Y., ElNaggar, M., Sze, S. K., Oh, H. B., Begley, T. P., McLafferty, F. W., Boshoff, H. I., & Barry, C. E. (2003) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(02)00913-3 · Cited by 79 · see citing works
Self-citationA New Approach for Plant Proteomics
Zabrouskov, V., Giacomelli, L., van Wijk, K. J., & McLafferty, F. W. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m300069-mcp200 · Cited by 73 · see citing works
αB‐crystallin exists as an independent protein in the heart and in the lens
Bhat, S. P., Horwitz, J., Srinivasan, A., & Ding, L. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16432.x · Cited by 70 · see citing works
Kellie, J. F., Catherman, A. D., Durbin, K. R., Tran, J. C., Tipton, J., Norris, J. L., Witkowski, C. E., Thomas, P. M., & Kelleher, N. (2011) · Analytical Chemistry · doi:10.1021/ac202384v · Cited by 62 · see citing works
Simpson, D. C., Ahn, S., Paša‐Tolić, L., Bogdanov, B., Mottaz, H. M., Vilkov, A. N., Anderson, G., Lipton, M. S. W., & Smith, R. D. (2006) · Electrophoresis · doi:10.1002/elps.200600037 · Cited by 57 · 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
Top-down Targeted Proteomics for Deep Sequencing of Tropomyosin Isoforms
Peng, Y., Chen, X., Zhang, H., Xu, Q., Hacker, T. A., & Ge, Y. (2012) · Journal of Proteome Research · doi:10.1021/pr301054n · Cited by 44 · see citing works
Self-citationIn-depth proteomic analysis of human tropomyosin by top-down mass spectrometry
Peng, Y., Yu, D., Gregorich, Z., Chen, X., Beyer, A. M., Gutterman, D. D., & Ge, Y. (2013) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-013-9352-y · Cited by 42 · see citing works
Self-citationGregorich, Z. R., Cai, W., Lin, Z., Chen, A. J., Peng, Y., Kohmoto, T., & Ge, Y. (2017) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2017.04.002 · Cited by 42 · see citing works
Self-citationTipton, J. D., Tran, J. C., Catherman, A. D., Ahlf, D. R., Durbin, K. R., Lee, J. E., Kellie, J. F., Kelleher, N. L., Hendrickson, C. L., & Marshall, A. G. (2012) · Analytical Chemistry · doi:10.1021/ac202651v · Cited by 40 · see citing works
Top‐down tandem mass spectrometry on RN ase A and B using a Q h/ FT ‐ ICR hybrid mass spectrometer
Bourgoin‐Voillard, S., Leymarie, N., & Costello, C. E. (2014) · PROTEOMICS · doi:10.1002/pmic.201300433 · Cited by 39 · see citing works
Carel, C., Marcoux, J., Réat, V., Parra, J., Latgé, G., Laval, F., Demange, P., Burlet-Schiltz, O., Milon, A., Daffé, M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617888114 · Cited by 36 · see citing works
Jin, Y., Wei, L., Cai, W., Lin, Z., Wu, Z., Peng, Y., Kohmoto, T., Moss, R. L., & Ge, Y. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00113 · 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
Ultrahigh pressure fast size exclusion chromatography for top‐down proteomics
Chen, X., & Ge, Y. (2013) · PROTEOMICS · doi:10.1002/pmic.201200594 · Cited by 33 · see citing works
Self-citationEffective Top-Down LC/MS+ Method for Assessing Actin Isoforms as a Potential Cardiac Disease Marker
Chen, Y.-C., Ayaz-Guner, S., Peng, Y., Lane, N. M., Locher, M. R., Kohmoto, T., Larsson, L., Moss, R. L., & Ge, Y. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b01745 · Cited by 31 · see citing works
Self-citationWood, T. D., Chen, L. H., White, C. B., Babbitt, P. C., Kenyon, G. L., & McLafferty, F. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.25.11451 · Cited by 30 · see citing works
Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top-down Mass Spectrometry
Lin, Z.-Q., Guo, F., Gregorich, Z., Sun, R.-X., Zhang, H., Hu, Y., Shanmuganayagam, D., & Ge, Y. (2018) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-018-1925-y · Cited by 15 · see citing works
Self-citationSize Exclusion High-Performance Liquid Chromatography of Small Solutes
Alpert, A. J. (1999) · Elsevier eBooks · doi:10.1016/b978-012765555-0/50009-9 · Cited by 15 · see citing works
FABP3 as Biomarker of Heart Pathology
Catalucci, D., Latronico, M. V. G., & Condorelli, G. (2015) · Biomarkers in disease · doi:10.1007/978-94-007-7696-8_22 · Cited by 6 · see citing works
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Schaffer, L. V., Millikin, R. J., Miller, R. M., Anderson, L. C., Fellers, R. T., Ge, Y., Kelleher, N. L., LeDuc, R. D., Liu, X., Payne, S. H., et al. (2019) · PROTEOMICS · doi:10.1002/pmic.201800361 · Cited by 209 · see citing works
Self-citationNovel Strategies to Address the Challenges in Top-Down Proteomics
Melby, J. A., Roberts, D. S., Larson, E. J., Brown, K. A., Bayne, E. F., Jin, S., & Ge, Y. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.1c00099 · Cited by 191 · see citing works
Self-citationRoberts, D. S., Loo, J. A., Tsybin, Y. O., Liu, X., Wu, S., Chamot-Rooke, J., Agar, J. N., Paša-Tolić, L., Smith, L. M., & Ge, Y. (2024) · Nature Reviews Methods Primers · doi:10.1038/s43586-024-00318-2 · Cited by 154 · see citing works
Self-citationHigh-throughput quantitative top-down proteomics
Cupp‐Sutton, K. A., & Wu, S. (2020) · Molecular Omics · doi:10.1039/c9mo00154a · Cited by 116 · see citing works
Ion Activation Methods for Peptides and Proteins
Macias, L. A., Santos, I. C., & Brodbelt, J. S. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.9b04859 · Cited by 107 · see citing works
Proton Transfer Charge Reduction Enables High-Throughput Top-Down Analysis of Large Proteoforms
Huguet, R., Mullen, C., Srzentić, K., Greer, J. B., Fellers, R. T., Zabrouskov, V., Syka, J. E. P., Kelleher, N. L., & Fornelli, L. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b03925 · Cited by 94 · see citing works
Roberts, D. S., Mann, M. W., Melby, J. A., Larson, E. J., Zhu, Y., Brasier, A. R., Jin, S., & Ge, Y. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c02713 · Cited by 73 · see citing works
Self-citationZhou, M., Uwugiaren, N., Williams, S. M., Moore, R. J., Zhao, R., Goodlett, D., Dapic, I., Paša-Tolić, L., & Zhu, Y. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c00467 · Cited by 62 · see citing works
Liu, R., Xia, S., & Li, H. (2022) · Mass Spectrometry Reviews · doi:10.1002/mas.21793 · Cited by 59 · see citing works
Kaulich, P. T., Jeong, K., Kohlbacher, O., & Tholey, A. (2024) · Nature Methods · doi:10.1038/s41592-024-02481-6 · Cited by 38 · see citing works
Brown, K. A., Tucholski, T., Alpert, A. J., Eken, C., Wesemann, L., Kyrvasilis, A., Jin, S., & Ge, Y. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c02533 · Cited by 35 · see citing works
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Gomes, F. P., Durbin, K. R., Schauer, K. L., Nwachukwu, J., Kobylski, R. R., Njeri, J., Seath, C. P., Saviola, A. J., McClatchy, D. B., Diedrich, J. K., et al. (2025) · Nature Chemical Biology · doi:10.1038/s41589-025-01866-8 · Cited by 34 · see citing works
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Su, T., Hollas, M. A. R., Fellers, R. T., & Kelleher, N. L. (2023) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-020722-044021 · Cited by 37 · see citing works
Stastna, M. (2024) · The FEBS Journal · doi:10.1111/febs.17108 · Cited by 28 · see citing works
Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry for Characterizing Proteoforms
Tucholski, T., & Ge, Y. (2020) · Mass spectrometry reviews (Print) · doi:10.1002/mas.21653 · Cited by 18 · see citing works
Self-citationChapman, E. A., Roberts, D. S., Tiambeng, T. N., Andrews, J., Wang, M.-D., Reasoner, E. A., Melby, J. A., Li, B. H., Kim, D., Alpert, A. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43321-z · Cited by 28 · see citing works
Self-citationKellie, J. F., Tran, J. C., Jian, W., Jones, B. R., Mehl, J. T., Ge, Y., Henion, J. D., & Bateman, K. P. (2020) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.0c00270 · Cited by 28 · see citing works
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Habeck, T., & Lermyte, F. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220098 · Cited by 22 · see citing works
Wang, Q.-J., Xu, T., Fang, F., Wang, Q.-Y., Lundquist, P., & Sun, L.-L. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c02346 · Cited by 17 · see citing works
Shen, X., Xu, T., Hakkila, B., Hare, M. G., Wang, Q., Wang, Q., Beckman, J. S., & Sun, L. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.0c00484 · Cited by 22 · see citing works
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Takemori, A., Kaulich, P. T., Tholey, A., & Takemori, N. (2025) · Nature Protocols · doi:10.1038/s41596-024-01100-0 · Cited by 17 · see citing works
Guo, Y., Chowdhury, T., Seshadri, M., Cupp‐Sutton, K. A., Wang, Q., Yu, D., & Wu, S. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.2c00549 · Cited by 17 · see citing works
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Fischer, M. S., Rogers, H. T., Chapman, E. A., Jin, S., & Ge, Y. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.5c02341 · Cited by 13 · see citing works
Self-citationRamírez‐Sagredo, A., Sunny, A. T., Cupp‐Sutton, K. A., Chowdhury, T., Zhao, Z., Wu, S., & Chiao, Y. A. (2024) · Clinical Proteomics · doi:10.1186/s12014-024-09509-1 · Cited by 14 · see citing works
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Chapman, E. A., Li, B. H., Krichel, B., Chan, H., Buck, K. M., Roberts, D. S., & Ge, Y. (2024) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.3c00430 · Cited by 11 · see citing works
Self-citationCastro‐Perez, J. M., & Prakash, C. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-820018-6.00002-8 · Cited by 12 · see citing works
Deep Bottom-up Proteomics Enabled by the Integration of Liquid-Phase Ion Trap
Fu, X., Hong, J., Zhai, Y., Liu, K., & Xu, W. L. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c00532 · Cited by 10 · see citing works
Size Exclusion Chromatography Strategies and MASH Explorer for Large Proteoform Characterization
Tiambeng, T. N., Wu, Z., Melby, J. A., & Ge, Y. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2325-1_3 · Cited by 10 · see citing works
Self-citationCline, E. N., Alvarez, C., Duan, J., & Patrie, S. M. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c00396 · Cited by 8 · see citing works
Lee, J.-U., Kim, Y., Kim, W. Y., & Oh, H. B. (2020) · Physical Chemistry Chemical Physics · doi:10.1039/c9cp05433b · Cited by 8 · see citing works
Protein Interactome Profiling of Stable Molecular Complexes in Biomaterial Lysate
Mezentsev, Y., Ershov, P., Yablokov, E., Kaluzhskiy, L., Kupriyanov, K., Gnedenko, O., & Ivanov, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415697 · Cited by 4 · see citing works
Recent Advancements and Applications of Size Exclusion Chromatography in Modern Analysis
Bhatia, R., Kumari, Y., & Chopra, A. (2023) · Current Analytical Chemistry · doi:10.2174/1573411019666230526144816 · Cited by 6 · see citing works
Rogers, H. T., Melby, J. A., Ehlers, L. E., Fischer, M. S., Larson, E. J., Gao, Z., Rossler, K. J., Wang, D.-J., Alpert, A. J., & Ge, Y. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.3c05733 · Cited by 8 · see citing works
Self-citationChapman, E. A., Rogers, H. T., Gao, Z., Chan, H.-J., Alvarado, F. J., & Ge, Y. (2025) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2025.03.012 · Cited by 1 · see citing works
Self-citationComparative Analysis of Proteoform Clean‐Up Methods for In‐Depth Top‐Down Proteomics
Williams, A. A., Firenza, K. N., Carfagno, A. K., Kline, J. T., & Fornelli, L. (2025) · PROTEOMICS · doi:10.1002/pmic.70067 · Cited by 4 · see citing works
Melfi, M. T., Kanawati, B., Schmitt‐Kopplin, P., Macchia, L., Centonze, D., & Nardiello, D. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109919 · Cited by 3 · see citing works
Ion Activation Methods for Top-Down Proteomics.
Walker, J. N., & Brodbelt, J. (2026) · Mass spectrometry reviews (Print) · doi:10.1002/mas.70023 · Cited by 1 · see citing works
Deciphering Proteoform Landscape of Mammary Carcinoma by Top-Down Proteomics
Knott, S. J., Tucholski, T., Josyer, H., Inman, D., Friedl, A., Zhu, Y.-L., Ge, Y., & Ponik, S. (2025) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c01044 · Cited by 1 · see citing works
Self-citationApplication of Machine Learning in Pharmacoproteomics
Adutwum, L. A., Oppong, M. B., Lartey, M., & Opuni, K. F. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-64021-6_15 · Cited by 1 · see citing works
Proteoforms: General Concepts and Methodological Process for Identification
Araújo, J. D. S., & Machado, O. L. T. (2019) · Proteoforms - Concept and Applications in Medical Sciences · doi:10.5772/intechopen.89914 · Cited by 1 · see citing works
Proteomic applications for studies of bull fertility
Viana, A. G. D. A. (2022) · doi:10.47328/ufvbbt.2022.651
Recent Advances in Top-Down Proteomics for Proteoform Analysis
Yu, J., Kim, M.-J., & Park, H.-M. (2023) · KSBB Journal · doi:10.7841/ksbbj.2023.38.1.12
Methods for the Investigation of Protein–Ligands Interactions
Iacobucci, I., Cozzolino, F., Cipollone, I., & Monti, M. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-21638-0_8
A Draft Map of E. coli Proteoforms
Colón-Rosado, J. A., Fang, F., & Sun, L.-L. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.6c03571
- Authors
- Tucholski, T., Knott, S. J., Chen, B., Pistono, P., Lin, Z., & Ge, Y.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Ge, Ying
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-02-13
- Volume
- 91
- Issue
- 6
- Pages
- 3835-3844
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC6545233
- OpenAlex
- W2914139080
- Cited by
- 49
- References
- 60
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 5 · 2018: 1
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01 GM117058, R01 GM125085)
- NIH Office of the Director (S10 OD018475)
- National Heart, Lung, and Blood Institute (R01 HL096971, R01 HL109810)
- Division of Human Resource Development (HRD-1612530)
- Division of Graduate Education (DGE-1747503)
- 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, FT-ICR mass spectrometry, proteoforms, isotopic resolution, electron capture dissociation, post-translational modification
- MeSH terms
- Chromatography, Gel, Fourier Analysis, Humans, Myocardium, Mass Spectrometry, Cyclotrons, Proteomics
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