Top Down proteomics: Facts and perspectives
Open accessAbstract
The rise of the "Top Down" method in the field of mass spectrometry-based proteomics has ushered in a new age of promise and challenge for the characterization and identification of proteins. Injecting intact proteins into the mass spectrometer allows for better characterization of post-translational modifications and avoids several of the serious "inference" problems associated with peptide-based proteomics. However, successful implementation of a Top Down approach to endogenous or other biologically relevant samples often requires the use of one or more forms of separation prior to mass spectrometric analysis, which have only begun to mature for whole protein MS. Recent advances in instrumentation have been used in conjunction with new ion fragmentation using photons and electrons that allow for better (and often complete) protein characterization on cases simply not tractable even just a few years ago. Finally, the use of native electrospray mass spectrometry has shown great promise for the identification and characterization of whole protein complexes in the 100 kDa to 1 MDa regime, with prospects for complete compositional analysis for endogenous protein assemblies a viable goal over the coming few years.
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Bottom-up approaches are high-throughput, but critical information about PTMs and subunit protein assemblies is generally lost after proteolysis.
“This approach is well-known for its high-throughput performance; however, critical information about PTMs and subunit protein assemblies (via non-covalent interactions) is generally lost after proteolysis14,31.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [31]
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MethodMass spectrometry of membrane transporters reveals subunit stoichiometry and interactions
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Analysis of Intact Monoclonal Antibody IgG1 by Electron Transfer Dissociation Orbitrap FTMS
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Self-citationDual-Pressure Linear Ion Trap Mass Spectrometer Improving the Analysis of Complex Protein Mixtures
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Self-citationBondarenko, P. V., Second, T. P., Zabrouskov, V., Makarov, A., & Zhang, Z. (2009) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.03.020 · 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
McAlister, G. C., Berggren, W. T., Griep‐Raming, J., Horning, S. R., Makarov, A., Phanstiel, D., Stafford, G. C., Swaney, D. L., Syka, J. E. P., Zabrouskov, V., et al. (2008) · Journal of Proteome Research · doi:10.1021/pr800264t · Cited by 145 · see citing works
Wilcox, B., Hendrickson, C., & Marshall, A. (2002) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(02)00622-0 · Cited by 139 · cited 1× · see citing works
“Significant advances to FT-ICR technology, often focused on improving the analysis of intact proteins, included increases in magnetic field [88,89], addition of a resolving quadrupole for mass selection [90], and an accumulation octupole for ion storage before transmission to the ICR cell [91,92].”
Hogan, C. J., Ruotolo, B., Robinson, C., & de la Mora, J. F. (2011) · Journal of Physical Chemistry B · doi:10.1021/jp109172k · Cited by 127 · see citing works
Cation-exchange chromatography of peptides on poly(2-sulfoethyl aspartamide)-silica.
Alpert, A. J., & Andrews, P. (1988) · Journal of Chromatography A · doi:10.1016/s0021-9673(00)94785-x · Cited by 127 · cited 1×
“In contrast with RPLC, HILIC utilizes a polar stationary phase and gradients of increasing water content, resulting in the elution of more hydrophobic species first [26,27].”
BackgroundParks, B. A., Jiang, L., Thomas, P. M., Wenger, C. D., Roth, M. J., Boyne, M. T., Burke, P. V., Kwast, K. E., & Kelleher, N. L. (2007) · Analytical Chemistry · doi:10.1021/ac070553t · Cited by 123 · cited 2× · see citing works
“proteome [36] and a variety of membrane proteins [96,97].”
BackgroundMethodSelf-citationMultiplexed size separation of intact proteins in solution phase for mass spectrometry.
Tran, J. C., & Doucette, A. (2009) · Analytical Chemistry · doi:10.1021/ac900729r · Cited by 123 · cited 1× · see citing works
“It was shown that the device could be used as a first dimension of separation prior to a multiplexed version of GELFrEE, analogous to a twodimensional gel separation [55].”
MethodWeb and database software for identification of intact proteins using "top down" mass spectrometry.
Taylor, G. K., Kim, Y.-B., Forbes, A. J., Meng, F.-Y., McCarthy, R. T., & Kelleher, N. (2003) · Analytical Chemistry · doi:10.1021/ac0341721 · Cited by 119 · see citing works
Self-citationBalaguer, E., & Neusüß, C. (2006) · Analytical Chemistry · doi:10.1021/ac060376g · Cited by 117 · cited 1× · see citing works
“Notable examples include the detection of the α and β subunits of hemoglobin from a single erythrocyte [60] and the detection of various protein glycoforms of erythropoietin, fetuin, and α1-acid glycoprotein [61].”
BackgroundHigh-resolution tandem mass spectrometry of large biomolecules.
Loo, J., Quinn, J. P., Ryu, S. I., Henry, K. D., Senko, M., & McLafferty, F. (1992) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.89.1.286 · Cited by 105 · cited 1× · see citing works
“The same instrument was also utilized to perform collision-induced dissociation (CID) and nozzle-skimmer dissociation (NSD) of ubiquitin, using the high resolving power of the instrument to determine charge state and identity of the fragment ions [83].”
MethodA Robust Two-Dimensional Separation for Top-Down Tandem Mass Spectrometry of the Low-Mass Proteome
Lee, J. E., Kellie, J. F., Tran, J. C., Tipton, J., Catherman, A. D., Thomas, H. M., Ahlf, D. R., Durbin, K. R., Vellaichamy, A., Ntai, I., et al. (2009) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.08.001 · Cited by 104 · cited 3× · see citing works
“Polymeric reversed-phase materials, offering increased mechanical strength, uniform hydrophobicity, and high recovery, have also been utilized for the separation of intact proteins [13,22,23,24].”
BackgroundMethodSelf-citationGene-specific characterization of human histone H2B by electron capture dissociation.
Siuti, N., Roth, M. J., Mizzen, C., Kelleher, N., & Pesavento, J. J. (2006) · Journal of Proteome Research · doi:10.1021/pr050268v · Cited by 101 · cited 1× · see citing works
“The potential for achieving full protein characterization has made the Top Down mass spectrometry approach extremely useful for analysis of single proteins or simple mixtures of significant biological interest [6,7,8,9,10,11].”
BackgroundSelf-citationAnalysis of Intact Protein Isoforms by Mass Spectrometry
Tipton, J. D., Tran, J. C., Catherman, A. D., Ahlf, D. R., Durbin, K. R., & Kelleher, N. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.239442 · Cited by 99 · cited 1× · see citing works
“Extremely high resolution may be required to distinguish disulfide bridges (Δm = 2 Da), deamidation (Δm = 1 Da), trimethylation versus acetylation (Δm = 39 mDa), and phosphorylation versus sulfation (Δm = 10 mDa) [70].”
BackgroundSelf-citationKellie, J. F., Tran, J. C., Lee, J. E., Ahlf, D. R., Thomas, H. M., Ntai, I., Catherman, A. D., Durbin, K. R., Zamdborg, L., Vellaichamy, A., et al. (2010) · Molecular BioSystems · doi:10.1039/c000896f · Cited by 99 · cited 1× · see citing works
“The great complexity within most proteomic samples requires that they be fractionated prior to introduction to the mass spectrometer [12].”
BackgroundSelf-citationZhang, D., Sweredoski, M. J., Graham, R. L. J., Hess, S. Y., & Shan, S. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.011585 · Cited by 98 · see citing works
Roth, M. J., Forbes, A. J., Boyne, M., Kim, Y.-B., Robinson, D., & Kelleher, N. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500064-mcp200 · Cited by 96 · cited 1× · see citing works
“has been utilized for a variety of Top Down proteomic studies [16,38,45,94].”
MethodSelf-citationVellaichamy, A., Tran, J. C., Catherman, A. D., Lee, J. E., Kellie, J. F., Sweet, S., Zamdborg, L., Thomas, P. M., Ahlf, D. R., Durbin, K. R., et al. (2010) · Analytical Chemistry · doi:10.1021/ac9021083 · Cited by 94 · cited 2× · see citing works
“Polymeric reversed-phase materials, offering increased mechanical strength, uniform hydrophobicity, and high recovery, have also been utilized for the separation of intact proteins [13,22,23,24].”
BackgroundSelf-citationPatrie, S. M., Charlebois, J. P., Whipple, D., Kelleher, N., Hendrickson, C., Quinn, J. P., Marshall, A., & Mukhopadhyay, B. (2004) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2004.04.031 · Cited by 93 · see citing works
Self-citationDefinition of the mitochondrial proteome by measurement of molecular masses of membrane proteins
Carroll, J., Fearnley, I., & Walker, J. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0607719103 · Cited by 92 · cited 2× · see citing works
“Membrane proteins extracted from bovine heart mitochondria have been fractionated using HILIC.”
MethodRyan, C., Souda, P., Bassilian, S., Ujwal, R., Zhang, J., Abramson, J., Ping, P., Durazo, A., Bowie, J., Hasan, S., et al. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900516-mcp200 · Cited by 91 · cited 1× · see citing works
“proteome [36] and a variety of membrane proteins [96,97].”
BackgroundHenry, K. D., & McLafferty, F. (1990) · Organic Mass Spectrometry · doi:10.1002/oms.1210250912 · Cited by 91 · cited 1× · see citing works
“8 Tesla (T) instrument, allowing for accurate mass determination [81,82].”
BackgroundCapriotti, A. L., Cavaliere, C., Foglia, P., Samperi, R., & Laganà, A. (2011) · Journal of Chromatography A · doi:10.1016/j.chroma.2011.05.094 · Cited by 91 · cited 6× · see citing works
“While a variety of liquid chromatography methods have been developed, reversed-phase liquid chromatography (RPLC), hydrophobic interaction liquid chromatography (HILIC), and ion exchange chromatography (IEX) are three of the most common liquid chromatography approaches applied to intact proteins [13].”
BackgroundMethodInfluentialEvaluation 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 · cited 2× · see citing works
“proteins from the H1299 human cancer cell line [51], followed by the identification of 1976 unique proteins from an H1299 cell line used to probe the proteome-wide difference in cellular senescence[118].”
BackgroundSelf-citationMazur, M. T., Cardasis, H. L., Spellman, D. S., Liaw, A., Yates, N. A., & Hendrickson, R. C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910776107 · Cited by 87 · see citing works
Mass spectrometric studies on noncovalent dimers of leucine zipper peptides
Li, Y., Hsieh, Y.-L., Henion, J., Senko, M., McLafferty, F., & Ganem, B. (1993) · Journal of the American Chemical Society · doi:10.1021/ja00071a058 · Cited by 84 · see citing works
Symmetrical gas-phase dissociation of noncovalent protein complexes via surface collisions.
Jones, C. M., Beardsley, R. L., Galhena, A. S., Dagan, S., Cheng, G., & Wysocki, V. (2006) · Journal of the American Chemical Society · doi:10.1021/ja064586m · Cited by 81 · see citing works
Chong, B. E., Yan, F., Lubman, D., & Miller, F. (2001) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.227 · Cited by 81 · cited 2× · see citing works
“variant of IEX which uses a change in pH rather than ionic strength to achieve elution, has been coupled to off-line RPLC for fractionation of intact proteins from breast cancer [17] and Methanosarcina acetivorans [38].”
BackgroundImproved fourier-transform ion-cyclotron-resonance mass spectrometry of large biomolecules
Beu, S., Senko, M., Quinn, J. P., & McLafferty, F. (1993) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(93)85077-b · Cited by 80 · see citing works
Proteomic profiling of intact proteins using WAX-RPLC 2-D separations and FTICR mass spectrometry.
Sharma, S., Simpson, D., Toliċ, N., Jaitly, N., Mayampurath, A., Smith, R. D., & Paša-Tolić, L. (2007) · Journal of Proteome Research · doi:10.1021/pr060354a · Cited by 77 · cited 1× · see citing works
“Anion exchange-RPLC has been utilized for the Top Down study of Shewanella oneidensis [35], yeast [36], and human leukocytes [37].”
MethodTop 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 · cited 2× · see citing works
“It should also be noted that the LTQ Velos has also been coupled to a 12 T FT-ICR mass spectrometer for Top Down analysis [52], however the instrument has not been commercialized and no other uses of such an instrument have been reported.”
BackgroundMethodSelf-citationEdwards, R., Griffiths, P., Bunch, J., & Cooper, H. (2012) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-012-0477-9 · Cited by 75 · see citing works
Resemann, A., Wunderlich, D., Rothbauer, U., Warscheid, B., Leonhardt, H., Fuchser, J., Kuhlmann, K., & Suckau, D. (2010) · Analytical Chemistry · doi:10.1021/ac1000515 · Cited by 68 · cited 1×
“The potential for achieving full protein characterization has made the Top Down mass spectrometry approach extremely useful for analysis of single proteins or simple mixtures of significant biological interest [6,7,8,9,10,11].”
BackgroundMillea, K. M., Krull, I. S., Cohen, S. A., Gebler, J. C., & Berger, S. J. (2005) · Journal of Proteome Research · doi:10.1021/pr050278w · Cited by 67 · see citing works
“Proteotyping”: Population Proteomics of Human Leukocytes Using Top Down Mass Spectrometry
Roth, M. J., Parks, B. A., Ferguson, J. T., Boyne, M. T., & Kelleher, N. L. (2008) · Analytical Chemistry · doi:10.1021/ac800141g · Cited by 65 · cited 2× · see citing works
“A 12 T version of the instrument has been utilized for increased throughput studies using the automated on-line/offline RPLC-MS platform for the study of HeLa nuclei [22], human leukocytes [37], and M.”
MethodSelf-citationYang, L.-Y., Lee, C. S., Hofstadler, S., Paša-Tolić, L., & Smith, R. D. (1998) · Analytical Chemistry · doi:10.1021/ac980224o · Cited by 64 · 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 · cited 1× · see citing works
“In the last few years, several papers have been published using GELFrEE for molecular-weight based fractionation for Top Down proteomics, allowing for increased throughput and number of identifications [24,49,50,51,52].”
BackgroundSelf-citationPatrie, S. M., Ferguson, J. T., Robinson, D. E., Whipple, D., Rother, M., Metcalf, W. W., & Kelleher, N. L. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500219-mcp200 · Cited by 62 · cited 2× · see citing works
“variant of IEX which uses a change in pH rather than ionic strength to achieve elution, has been coupled to off-line RPLC for fractionation of intact proteins from breast cancer [17] and Methanosarcina acetivorans [38].”
BackgroundMethodSelf-citationPesavento, J. J., Garcia, B., Streeky, J. A., Kelleher, N., & Mizzen, C. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600404-mcp200 · Cited by 61 · cited 1× · see citing works
“[28,29] HILIC has also been extensively applied for the separation of modified histone forms prior to Top Down mass spectrometry [30,31,32].”
MethodSelf-citationIdentification of membrane proteins by tandem mass spectrometry of protein ions
Carroll, J., Altman, M. C., Fearnley, I., & Walker, J. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0706817104 · Cited by 60 · cited 2× · see citing works
“Membrane proteins extracted from bovine heart mitochondria have been fractionated using HILIC.”
MethodAnalysis of 953 Human Proteins from a Mitochondrial HEK293 Fraction by Complexome Profiling
Wessels, H., Vogel, R. O., Lightowlers, R., Spelbrink, J., Rodenburg, R., van den Heuvel, L. P., van Gool, A. V., Gloerich, J., Smeitink, J., & Nijtmans, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068340 · Cited by 59 · see citing works
Precursor ion independent algorithm for top-down shotgun proteomics
Tsai, Y. S., Scherl, A., Shaw, J. L., Mackay, C. L., Shaffer, S. A., Langridge‐Smith, P. R. R., & Goodlett, D. R. (2009) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.07.024 · Cited by 59 · see citing works
Wall, D., Kachman, M. T., Gong, S.-Y., Parus, S., Long, M. W., & Lubman, D. (2001) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.421 · Cited by 57 · cited 2×
“A preparative-scale Rotofor, capable of separating ~1 g of protein within 55 mL of buffer, and the mini-Rotofor, a smaller version of the device which can hold ~15 mL of solution, have been used for the fractionation of the human erythroleukemia cell line proteome prior to NPS-RPLC-MS [18,19,20].”
BackgroundMethodZhou, F., & Johnston, M. (2004) · Analytical Chemistry · doi:10.1021/ac035446n · Cited by 54 · cited 1× · see citing works
“cIEF has also been coupled to RPLC-MS, which allowed for a second dimension of separation and the removal of ampholytes which can cause significant ionization suppression [68].”
MethodBereszczak, J. Z., Barbu, I., Tan, M., Xia, M., Jiang, X., van Duijn, E., & Heck, A. J. R. (2012) · Journal of Structural Biology · doi:10.1016/j.jsb.2012.01.005 · Cited by 53 · see citing works
Théberge, R., Infusini, G., Tong, W., McComb, M. E., & Costello, C. E. (2010) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2010.08.012 · Cited by 44 · see citing works
Moini, M., & Huang, H.-Y. (2004) · Electrophoresis · doi:10.1002/elps.200305906 · Cited by 42 · see citing works
Thangaraj, B., Ryan, C., Souda, P., Krause, K., Faull, K. F., Weber, A. P. M., Fromme, P., & Whitelegge, J. P. (2010) · Proteomics · doi:10.1002/pmic.201000190 · Cited by 41 · cited 1× · see citing works
“proteome [36] and a variety of membrane proteins [96,97].”
BackgroundTop-down proteomics reveals novel protein forms expressed in methanosarcina acetivorans
Ferguson, J. T., Wenger, C. D., Metcalf, W. W., & Kelleher, N. L. (2009) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.05.014 · Cited by 41 · cited 1× · see citing works
“acetivorans [98] as well as the GELFrEE platform for the analysis of S.”
MethodSelf-citationRoth, M. J., Plymire, D. A., Chang, A. N., Kim, J., Maresh, E. M., Larson, S. E., & Patrie, S. M. (2011) · Analytical Chemistry · doi:10.1021/ac202339x · Cited by 41 · cited 1× · see citing works
“Use of superficially porous particles, which contain a nonporous silica core and a porous shell, has been reported for protein separations, offering similar efficiency to that of nonporous columns but with reduced back pressure and improved loading capacity [21].”
BackgroundZhou, F., Hanson, T. E., & Johnston, M. (2007) · Analytical Chemistry · doi:10.1021/ac071147c · Cited by 40 · cited 1× · see citing works
“Using this platform, 1200 polypeptides/proteins from Chlorobium tepidum were detected over an eight hour separation [69].”
MethodDoerr, A. (2008) · Nature Methods · doi:10.1038/nmeth1162 · Cited by 40 · see citing works
Belov, M. E., Nikolaev, E. N., Anderson, G., Auberry, K., Harkewicz, R., & Smith, R. D. (2001) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(00)00198-7 · Cited by 40 · cited 1× · see citing works
“Significant advances to FT-ICR technology, often focused on improving the analysis of intact proteins, included increases in magnetic field [88,89], addition of a resolving quadrupole for mass selection [90], and an accumulation octupole for ion storage before transmission to the ICR cell [91,92].”
Tipton, 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 · cited 1× · see citing works
“This instrument was also utilized for analysis of GELFrEE fractions, using the improvement in sensitivity and resolution for the detection and identification of higher molecular weight proteins [23,100].”
MethodSelf-citationStructural characterization of intact antibodies by high‐resolution LTQ Orbitrap mass spectrometry
Zhang, J., Liu, H., & Katta, V. (2009) · Journal of Mass Spectrometry · doi:10.1002/jms.1700 · Cited by 40 · see citing works
Tran, J. C., & Doucette, A. (2008) · Journal of Proteome Research · doi:10.1021/pr700677u · Cited by 37 · cited 1× · see citing works
“Another variant of solution isoelectric focusing (sIEF) for protein fractionation was reported in 2008 [54].”
BackgroundErales, J., Gontero, B., Whitelegge, J. P., & Halgand, F. (2008) · Biochemical Journal · doi:10.1042/bj20082004 · Cited by 36 · cited 1× · see citing works
“The potential for achieving full protein characterization has made the Top Down mass spectrometry approach extremely useful for analysis of single proteins or simple mixtures of significant biological interest [6,7,8,9,10,11].”
BackgroundAlpert, A. J. (1988) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)94030-0 · Cited by 35 · cited 1×
“In contrast with RPLC, HILIC utilizes a polar stationary phase and gradients of increasing water content, resulting in the elution of more hydrophobic species first [26,27].”
BackgroundDurbin, 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-citationVersatile Online−Offline Engine for Automated Acquisition of High-Resolution Tandem Mass Spectra
Wenger, C. D., Boyne, M. T., Ferguson, J. T., Robinson, D. E., & Kelleher, N. L. (2008) · Analytical Chemistry · doi:10.1021/ac8010704 · Cited by 33 · cited 4× · see citing works
“Polymeric reversed-phase materials, offering increased mechanical strength, uniform hydrophobicity, and high recovery, have also been utilized for the separation of intact proteins [13,22,23,24].”
BackgroundMethodInfluentialSelf-citationDavidsson, P., & Nilsson, C. L. (1999) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(99)00197-x · Cited by 32 · cited 1× · see citing works
“Proteins can be electroeluted from SDS-PAGE gels using an orthogonally applied electric field to the gel; however few studies have been reported, likely due to poor recovery [44].”
BackgroundKovářová, H., Halada, P., Man, P., Golovliov, I. R., Kročová, Z., Špaček, J., Porkertová, S., & Nečasová, R. (2002) · PROTEOMICS · doi:10.1002/1615-9861(200201)2:1 · Cited by 31 · see citing works
Du, Y., Meng, F.-Y., Patrie, S. M., Miller, L. M., & Kelleher, N. (2004) · Journal of Proteome Research · doi:10.1021/pr0499489 · Cited by 27 · cited 2× · see citing works
“An improvement to this original separation used a mini prep-cell, featuring a 7 mm gel column, rather than a 37 mm column, coupled to a 320 μm C4 column allowing for 15 to 300-fold less sample loading as well some on-line analysis [45].”
MethodSelf-citationUse of rotofor preparative isoelectrofocusing cell in protein purification procedure
Ayala, A., Parrado, J., & Machado, A. (1998) · Applied Biochemistry and Biotechnology · doi:10.1007/bf02786017 · Cited by 26 · cited 1×
“The Rotofor device uses an IEF separation but within an open channel, where the pH gradient is formed through the use of carrier ampholytes in solution between an acidic anode and a basic cathode [53].”
MethodWu, S., Brown, R. N., Payne, S., Meng, D., Zhao, R., Tolić, N., Cao, L., Shukla, A. K., Monroe, M. E., Moore, R. J., et al. (2013) · International Journal of Proteomics · doi:10.1155/2013/279590 · Cited by 22 · see citing works
Global histone profiling by LC–FTMS after inhibition and knockdown of deacetylases in human cells
Li, M., Jiang, L., & Kelleher, N. L. (2009) · Journal of Chromatography B · doi:10.1016/j.jchromb.2009.09.042 · Cited by 21 · cited 1× · see citing works
“The potential for achieving full protein characterization has made the Top Down mass spectrometry approach extremely useful for analysis of single proteins or simple mixtures of significant biological interest [6,7,8,9,10,11].”
BackgroundSelf-citationKappes, T., Schnierle, P., & Hauser, P. C. (2000) · Electrophoresis · doi:10.1002/(sici)1522-2683(20000401)21:7 · Cited by 19 · see citing works
Hofstadler, S., Severs, J., Smith, R. D., Swanek, F., & Ewing, A. (1996) · doi:10.1002/jhrc.1240191105 · Cited by 17 · cited 1×
“Notable examples include the detection of the α and β subunits of hemoglobin from a single erythrocyte [60] and the detection of various protein glycoforms of erythropoietin, fetuin, and α1-acid glycoprotein [61].”
BackgroundWall, D., Parus, S., & Lubman, D. (2001) · Journal of Chromatography B: Biomedical Sciences and Applications · doi:10.1016/s0378-4347(01)00382-6 · Cited by 12 · cited 2×
“A preparative-scale Rotofor, capable of separating ~1 g of protein within 55 mL of buffer, and the mini-Rotofor, a smaller version of the device which can hold ~15 mL of solution, have been used for the fractionation of the human erythroleukemia cell line proteome prior to NPS-RPLC-MS [18,19,20].”
BackgroundMethod
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Gutiérrez, J., Calvete, J., Habib, A., Harrison, R., Williams, D. J., & Warrell, D. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.63 · Cited by 752 · see citing works
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High-Resolution Native Mass Spectrometry
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Quantitative Proteomic Analysis of Histone Modifications
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A Review on Quantitative Multiplexed Proteomics
Pappireddi, N., Martin, L., & Wühr, M. (2019) · ChemBioChem · doi:10.1002/cbic.201800650 · Cited by 299 · see citing works
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Illuminating the dark phosphoproteome
Needham, E. J., Parker, B. L., Burykin, T., James, D. E., & Humphrey, S. J. (2019) · Science Signaling · doi:10.1126/scisignal.aau8645 · Cited by 322 · see citing works
Highly Sensitive and Multiplexed Protein Measurements
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Beyond mass spectrometry, the next step in proteomics
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Ultraviolet Photodissociation Mass Spectrometry for Analysis of Biological Molecules
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Identification and Quantification of Proteoforms by Mass Spectrometry
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-citationIon Activation Methods for Peptides and Proteins
Brodbelt, J. S. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04563 · Cited by 245 · see citing works
Update: Post-translational protein modifications in plant metabolism
Friso, G., & van Wijk, K. J. (2015) · PLANT PHYSIOLOGY · doi:10.1104/pp.15.01378 · Cited by 178 · see citing works
“The identification, localization, and quantification of different combinations of PTMs on the same protein can sometimes be better solved by so-called top-down or middle-down proteomics, as opposed to the more common bottom-up proteomics (Lanucara and Eyers, 2013; Catherman et al., 2014).”
BackgroundNovel 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
Review: Detection and quantification of proteins in human urine
Aitekenov, S., Gaipov, A., & Bukasov, R. (2020) · Talanta · doi:10.1016/j.talanta.2020.121718 · Cited by 181 · see citing works
Pagel, O., Loroch, S., Sickmann, A., & Zahedi, R. P. (2015) · Expert Review of Proteomics · doi:10.1586/14789450.2015.1042867 · Cited by 161 · see citing works
“For a comprehensive overview of this fascinating and still emerging field, excellent reviews by the groups of MacLafferty and Kelleher [209,210] can be referred to.”
BackgroundProteomic insights into extracellular vesicle biology – defining exosomes and shed microvesicles
Greening, D. W., Xu, R., Gopal, S. K., Rai, A., & Simpson, R. J. (2016) · Expert Review of Proteomics · doi:10.1080/14789450.2017.1260450 · Cited by 159 · see citing works
Protein identification strategies in MALDI imaging mass spectrometry: a brief review
Ryan, D. J., Spraggins, J. M., & Caprioli, R. M. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.10.023 · Cited by 180 · see citing works
Proteins in Art, Archaeology, and Paleontology: From Detection to Identification
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Toward an Optimized Workflow for Middle-Down Proteomics
Cristobal, A., Marino, F., Post, H., van den Toorn, H. W. P., Mohammed, S., & Heck, A. J. R. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.6b03756 · Cited by 130 · see citing works
Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research
Gomes, F. P., & Yates, J. R. (2019) · Mass Spectrometry Reviews · doi:10.1002/mas.21599 · Cited by 112 · see citing works
A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications
Rogstad, S., Faustino, A. M., Ruth, A., Keire, D. A., Boyne, M., & Park, J. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-016-1531-9 · Cited by 110 · see citing works
Petras, D., Heiss, P., Süßmuth, R. D., & Calvete, J. J. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00305 · Cited by 102 · see citing works
Recent applications of capillary electromigration methods to separation and analysis of proteins
Štěpánová, S., & Kašička, V. (2016) · Analytica Chimica Acta · doi:10.1016/j.aca.2016.06.006 · Cited by 114 · see citing works
“Peptide mapping is frequently employed also in proteomic analyses by CE methods as shown in recent reviews on top-down [16,17] and bottom-up proteomics [14,17,159].”
MethodOmics-Driven Biotechnology for Industrial Applications
Amer, B., & Baidoo, E. E. K. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.613307 · Cited by 148 · see citing works
“Besides that, top-down is less sensitive and has a lower throughput than a bottom-up approach (Catherman et al., 2014).”
BackgroundTop-Down Proteomics and the Challenges of True Proteoform Characterization
Po, A., & Eyers, C. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.3c00416 · Cited by 94 · see citing works
Sunagar, K., Morgenstern, D., Reitzel, A. M., & Moran, Y. (2015) · Journal of Proteomics · doi:10.1016/j.jprot.2015.09.015 · Cited by 104 · see citing works
Middle-Down Mass Spectrometry Enables Characterization of Branched Ubiquitin Chains
Valkevich, E. M., Sanchez, N. A., Ge, Y., & Strieter, E. R. (2014) · Biochemistry · doi:10.1021/bi5006305 · Cited by 89 · see citing works
Lee, P. Y., Saraygord-Afshari, N., & Low, T. (2019) · Journal of Chromatography A · doi:10.1016/j.chroma.2019.460763 · Cited by 78
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. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00797 · Cited by 76 · see citing works
Self-citationAn integrative omics perspective for the analysis of chemical signals in ecological interactions
Brunetti, A. E., Neto, F. C., Vera, M. C., Taboada, C., Pavarini, D. P., Bauermeister, A., & Lopes, N. P. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00368d · Cited by 96 · see citing works
pTop 1.0: A High-Accuracy and High-Efficiency Search Engine for Intact Protein Identification
Sun, R.-X., Luo, L., Wu, L., Wang, R.-M., Zeng, W.-F., Chi, H., Liu, C., & He, S.-M. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.5b03963 · Cited by 71 · see citing works
Suttapitugsakul, S., Xiao, H., Smeekens, J. M., & Wu, R. (2017) · Molecular BioSystems · doi:10.1039/c7mb00393e · Cited by 103 · see citing works
Constructing comprehensive venom proteome reference maps for integrative venomics
Eichberg, S., Sanz, L., Calvete, J. J., & Plá, D. (2015) · Expert Review of Proteomics · doi:10.1586/14789450.2015.1073590 · Cited by 72 · see citing works
“Top-down mass spectrometry has the potential to eliminate this shortcoming [90,91].”
BackgroundEnhancing top-down proteomics of brain tissue with FAIMS
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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
Physicochemical characterization of biopharmaceuticals
Parr, M. K., Montacir, O., & Montacir, H. (2016) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2016.05.028 · Cited by 80 · see citing works
“The top-down approach enables a comprehensive analysis of the protein sequence almost without prior sample preparation [155, 156].”
BackgroundPetras, D., Heiss, P., Harrison, R. A., Süßmuth, R. D., & Calvete, J. J. (2016) · Journal of Proteomics · doi:10.1016/j.jprot.2016.06.018 · Cited by 71 · see citing works
Štěpánová, S., & Kašička, V. (2015) · Journal of Separation Science · doi:10.1002/jssc.201500973 · Cited by 70 · see citing works
High-throughput quantitative top-down proteomics
Cupp‐Sutton, K. A., & Wu, S. (2020) · Molecular Omics · doi:10.1039/c9mo00154a · Cited by 116 · see citing works
Activated 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
“By comparison, AI-ETD improves signal in product ion channels by 10–15% even for the most highly charge precursors, suggesting that (1) there is still some degree of significant gas-phase structure in more highly charge precursors and (2) that activation of the ion population during ETD reactions can improve reaction…”
BackgroundCassidy, L., Kaulich, P. T., Maaß, S., Bartel, J., Becher, D., & Tholey, A. (2021) · Proteomics · doi:10.1002/pmic.202100008 · Cited by 61 · see citing works
“Direct analysis at the intact protein level by TDP provides an alternative in which big advances in analytics have been achieved in the past few years [58,59].”
BackgroundNative vs Denatured: An in Depth Investigation of Charge State and Isotope Distributions
Kafader, J. O., Melani, R. D., Schachner, L. F., Ives, A. N., Patrie, S. M., Kelleher, N. L., & Compton, P. D. (2020) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.9b00040 · Cited by 51 · see citing works
Self-citationOverview and Considerations in Bottom-Up Proteomics
Miller, R. M., & Smith, L. (2022) · In Analysis · doi:10.1039/d2an01246d · Cited by 60 · see citing works
Automation of mass spectrometric detection of analytes and related workflows: A review
Elpa, D. P., Prabhu, G. R. D., Wu, S., Tay, K. S., & Urban, P. L. (2019) · Talanta · doi:10.1016/j.talanta.2019.120304 · Cited by 73 · see citing works
Elucidating Proteoform Families from Proteoform Intact-Mass and Lysine-Count Measurements
Shortreed, M. R., Frey, B. L., Scalf, M., Knoener, R. A., Cesnik, A. J., & Smith, L. M. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b01090 · Cited by 58 · see citing works
Triple-Stage Mass Spectrometry Unravels the Heterogeneity of an Endogenous Protein Complex
Ben-Nissan, G., Belov, M. E., Morgenstern, D., Levin, Y., Dym, O., Arkind, G., Lipson, C., Makarov, A. A., & Sharon, M. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00518 · Cited by 54 · see citing works
Middle-down approach: a choice to sequence and characterize proteins/proteomes by mass spectrometry
Pandeswari, P. B., & Sabareesh, V. (2019) · RSC Advances · doi:10.1039/c8ra07200k · Cited by 86 · see citing works
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Sequencing 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
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
“The analysis of intact proteins via Btop-down^ proteomics [1, 2] has grown in popularity in recent years and has been used to show proteomic differences associated with senescence [3–5], a model of bacterial infection [6], and myocardial infarction [7].”
MethodSelf-citationQuest for Missing Proteins: Update 2015 on Chromosome-Centric Human Proteome Project
Horvatovich, P. L., Lundberg, E. K., Chen, Y., Sung, T.-Y., He, F., Nice, E. C., Goode, R. J. A., Yu, S., Ranganathan, S., Baker, M. S., et al. (2015) · Journal of Proteome Research · doi:10.1021/pr5013009 · Cited by 54 · see citing works
Moreno, A. U., López, S. H., Reichert, B., Fernández, A. L., Guil, M. D. H., & Fernández-Alba, A. (2015) · Analytical Chemistry · doi:10.1021/ac5035852 · Cited by 55
Naldi, M., Baldassarre, M., Domenicali, M., Bartolini, M., & Caraceni, P. (2017) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2017.04.023 · Cited by 66 · see citing works
Enhanced Dissociation of Intact Proteins with High Capacity Electron Transfer Dissociation
Riley, N. M., Mullen, C., Weisbrod, C. R., Sharma, S., Senko, M. W., Zabrouskov, V., Westphall, M. S., Syka, J. E. P., & Coon, J. J. (2015) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-015-1306-8 · Cited by 59 · see citing works
“barrier to further progress in whole protein analysis [25–28].”
Zhu, Y., Piehowski, P. D., Kelly, R. T., & Qian, W.-J. (2018) · Expert Review of Proteomics · doi:10.1080/14789450.2018.1537787 · Cited by 50 · see citing works
Schubert, M., Walczak, M., Aebi, M., & Wider, G. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201502093 · Cited by 60 · see citing works
Háda, V., Bagdi, A., Bihari, Z., Timári, S. B., Fizil, Á., & Szántay, C. (2018) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2018.08.024 · Cited by 61 · see citing works
Wang, Z., Ma, H., Smith, K., & Wu, S. (2017) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2017.09.001 · Cited by 57 · see citing works
“, orbitrap and FTICR MS) has greatly advanced the field of top-down proteomics[6-8].”
BackgroundTop-down proteomics for the analysis of proteolytic events - Methods, applications and perspectives
Tholey, A., & Becker, A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.07.002 · Cited by 60 · see citing works
Coorssen, J., & Yergey, A. (2015) · Proteomes · doi:10.3390/proteomes3040440 · Cited by 51 · see citing works
“While still requiring extensive up-front protein resolution using multiple approaches, more recent MS-intensive top-down approaches have been refined to the point that substantial sequence coverage of a given purified protein is achievable [17,18].”
BackgroundMicrofluidics for Peptidomics, Proteomics, and Cell Analysis
Vitorino, R. M. P., Guedes, S. D. M., da Costa, J. P., & Kašička, V. (2021) · Nanomaterials · doi:10.3390/nano11051118 · Cited by 64 · see citing works
“Therefore, the target peptides and proteins usually need to be extracted or pre-isolated and/or preconcentrated from the sample matrix before analysis [101,102].”
BackgroundHuang, R., Chen, Z., He, L., He, N., Xi, Z., Li, Z., Deng, Y., & Zeng, X. (2017) · Theranostics · doi:10.7150/thno.20797 · Cited by 68 · see citing works
“while the top-down approach, on the other hand, both the intact proteins and fragment ions masses can be measured [30] (Figure 4).”
BackgroundA global view of the human post-translational modification landscape
Kitamura, N., & Galligan, J. J. (2023) · Biochemical Journal · doi:10.1042/bcj20220251 · Cited by 70 · see citing works
Ryan, D. J., Patterson, N. H., Putnam, N. E., Wilde, A. D., Weiss, A., Perry, W., Cassat, J. E., Skaar, E. P., Caprioli, R. M., & Spraggins, J. M. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05889 · Cited by 57 · see citing works
MALDI Detection of Exosomes: A Potential Tool for Cancer Studies
Zhu, Y., Pick, H. M., Gasilova, N., Li, X., Lin, T.-E. L., Laubli, H. P., Zippelius, A., Ho, P., & Girault, H. H. (2019) · Chem · doi:10.1016/j.chempr.2019.04.007 · Cited by 58 · see citing works
Elliott, A. G., Harper, C. C., Lin, H.-W., Susa, A. C., Xia, Z.-J., & Williams, E. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b01675 · Cited by 47 · see citing works
Proteoforms and their expanding role in laboratory medicine
Forgrave, L. M., Wang, M., Yang, D., & DeMarco, M. L. (2021) · Practical Laboratory Medicine · doi:10.1016/j.plabm.2021.e00260 · Cited by 46 · see citing works
“allows for full sequence coverage, including detection of protein sequence variations, and detection of PTMs on the whole protein level through the detection of a proteoform profile [30,31].”
BackgroundAdvances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve
Angel, P. M., Baldwin, H. S., Sen, D. G., Su, Y. R., Mayer, J. E., Bichell, D. P., & Drake, R. R. (2017) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2017.03.009 · Cited by 48 · see citing works
“In top down proteomic approaches, intact proteins are separated by LC and fragmented for sequence information without further enzymatic digestion [46].”
BackgroundHigh-throughput strategies for the discovery and engineering of enzymes for biocatalysis
Jacques, P., Béchet, M., Bigan, M., Caly, D. L., Châtaigné, G., Coutte, F., Flahaut, C., Heuson, E., Leclère, V., Lecouturier, D., et al. (2016) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-016-1690-x · Cited by 48 · see citing works
“Once the enzyme has been purified, its identification relies on the determination of amino acid sequence information carried out either by the physical, direct MS fragmentation [in source decay (ISD)] of the intact protein (top-down proteomics) [143, 144] or, after specific proteolysis of the enzyme, by MS fragmentati…”
Monazzah, M., Esfahani, M. N., & Enferadi, S. T. (2022) · Physiological and molecular plant pathology · doi:10.1016/j.pmpp.2022.101905 · Cited by 44
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. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b01638 · Cited by 43 · see citing works
Self-citationProgress and challenges in mass spectrometry-based analysis of antibody repertoires
Snapkov, I., Chernigovskaya, M., Sinitcyn, P. G., Quý, K. L., Nyman, T. A., & Greiff, V. (2021) · Trends in biotechnology · doi:10.1016/j.tibtech.2021.08.006 · Cited by 50 · see citing works
Maillard Proteomics: Opening New Pages
Soboleva, A., Schmidt, R., Vikhnina, M., Grishina, T., & Frolov, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122677 · Cited by 47 · see citing works
Accelerating the Field of Epigenetic Histone Modification Through Mass Spectrometry–Based Approaches
Lu, C., Coradin, M., Porter, E. G. P., & Garcia, B. A. (2020) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r120.002257 · Cited by 70 · see citing works
“in the top–down field, have described the history and fundamental concepts of top–down proteomics and discuss recent technical and conceptual advances (35, 36).”
BackgroundDobbs, J. M., Jenkins, M., & Burke, J. (2020) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.0c00283 · Cited by 42
Abiraami, T. V., Singh, S., & Nain, L. (2019) · Reviews in Environmental Science and Bio/Technology · doi:10.1007/s11157-019-09519-8 · Cited by 63 · see citing works
Sanders, J. D., Mullen, C., Watts, E., Holden, D. D., Syka, J. E. P., Schwartz, J. C., & Brodbelt, J. S. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b04026 · Cited by 53 · see citing works
It is time for top-down venomics
Melani, R., Nogueira, F. C. S., & Domont, G. (2017) · Journal of Venomous Animals and Toxins including Tropical Diseases · doi:10.1186/s40409-017-0135-6 · Cited by 42 · see citing works
“of charge states increasing signal-to-noise ratio because of lower number of channels to split ion intensity [16].”
BackgroundMethodProfiling microbial lignocellulose degradation and utilization by emergent omics technologies
Rosnow, J., Anderson, L. N., Nair, R. N., Baker, E., & Wright, A. (2017) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2016.1209158 · Cited by 42
“[51] Additionally, the ability to identify peptide fragments has improved greatly due to the depth of genome sequence and the bioinformatics tools available.”
BackgroundDang, X., Singh, A., Spetman, B. D., Nolan, K. D., Isaacs, J. S., Dennis, J. H., Dalton, S., Marshall, A. G., & Young, N. L. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00414 · Cited by 41 · see citing works
The effects of nonignorable missing data on label-free mass spectrometry proteomics experiments
O’Brien, J. J., Gunawardena, H. P., Paulo, J. A., Chen, X., Ibrahim, J. G., Gygi, S. P., & Qaqish, B. F. (2018) · The Annals of Applied Statistics · doi:10.1214/18-aoas1144 · Cited by 54 · see citing works
Recent Advances in Mass Spectrometry-Based Structural Elucidation Techniques
Ma, X. (2022) · Molecules · doi:10.3390/molecules27196466 · Cited by 57 · see citing works
Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches
Jafari, A., Babajani, A., & Rezaei–Tavirani, M. (2021) · Biomarker Insights · doi:10.1177/11772719211013352 · Cited by 48 · see citing works
Welker, M., & van Belkum, A. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02711 · Cited by 45 · see citing works
Taherkhani, A., Yekta, R. F., Mohseni, M., Saidijam, M., & Oskouie, A. A. (2019) · Proteome Science · doi:10.1186/s12953-019-0155-y · Cited by 39 · see citing works
“Massbased approaches are well suited in terms of sensitivity and throughput [17].”
Standardization of a protocol for shotgun proteomic analysis of saliva
Ventura, T. M. D. S., Ribeiro, N. R., Dionizio, A., Sabino, I. T., & Buzalaf, M. (2018) · Journal of Applied Oral Science · doi:10.1590/1678-7757-2017-0561 · Cited by 39
Characterization of microbial mixtures by mass spectrometry
Sandrin, T. R., & Demirev, P. A. (2017) · Mass Spectrometry Reviews · doi:10.1002/mas.21534 · Cited by 42 · see citing works
The Ups and Downs of Repeated Cleavage and Internal Fragment Production in Top-Down Proteomics
Lyon, Y. A., Riggs, D. L., Fornelli, L., Compton, P. D., & Julian, R. R. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-017-1823-8 · Cited by 39 · see citing works
Vehus, T., Ro̷berg-Larsen, H., Waaler, J., Aslaksen, S., Krauss, S., Wilson, S., & Lundanes, E. (2016) · Scientific Reports · doi:10.1038/srep37507 · Cited by 39 · see citing works
Liu, J., Yang, L., Liu, D., Wu, Q., Yu, Y., Huang, X., Li, J., & Liu, S. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.07.006 · Cited by 36 · see citing works
Identification of Splice Variants and Isoforms in Transcriptomics and Proteomics
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
“In contrast, TD proteomics analyzes either denatured or native intact proteins without enzymatic digestion (21).”
BackgroundSelf-citationThuy-Boun, P. S., Wang, A. Y., Crissien-Martinez, A., Xu, J. H., Chatterjee, S., Stupp, G. S., Su, A. I., Coyle, W., & Wolan, D. W. (2022) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2022.100197 · Cited by 43 · see citing works
“), perhaps genomics-agnostic, middle- and top-down proteomics sequencing could be applied (109, 110).”
Mass spectrometry and the cellular surfaceome.
Pauwels, J., Fijałkowska, D., Eyckerman, S., & Gevaert, K. (2021) · Mass spectrometry reviews (Print) · doi:10.1002/mas.21690 · Cited by 38 · see citing works
Mesleh, A. G., Abdulla, S. A., & El‐Agnaf, O. M. A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11010041 · Cited by 41 · see citing works
“Abbreviations ADHD Attention deficit hyperactivity disorder ADOS Autism Diagnostic Observation Schedule AGE Glycation end products ASD Autism spectrum disorder BA10 Brodmann area 10 CARS Childhood Autism Rating Scale CGH Comprehensive genomic hybridization CNV Copy number variant CSF Cerebrospinal fluid CVD Cardiovasc…”
BackgroundCiocan, C. A., Jurj, A. M., Buse, M., Gulei, D., Braicu, C., Ráduly, L., Cojocneanu, R., Pruteanu, L.-L., Iuga, C. A., Coza, O. F., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102576 · Cited by 43 · see citing works
“A frequently used method representative of the top-down strategy is protein ionization by matrix-assisted laser desorption ionization (MALDI) and mass measurement by time-of-flight (TOF) mass analyzer [32].”
MethodFoodomics: A novel approach for food microbiology
Xu, Y. (2017) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2017.05.012 · Cited by 50 · see citing works
Weisbrod, 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
“Intact protein analysis can provide structural information that cannot be obtained through traditional, bottom-up proteomics [2].”
- Authors
- Catherman, A. D., Skinner, O. S., & Kelleher, N. L.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Kelleher, Neil L.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 445
- Issue
- 4
- Pages
- 683-693
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC4103433
- OpenAlex
- W2070948666
- Cited by
- 507
- References
- 143
- Citations by year
- 2026: 21 · 2025: 32 · 2024: 31 · 2023: 37 · 2022: 48 · 2021: 49 · 2020: 49 · 2019: 46 · 2018: 41 · 2017: 59 · 2016: 38 · 2015: 42 · 2014: 14
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM067193)
- 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, post-translational modification, protein characterization, protein separation, protein complex identification
- MeSH terms
- Amino Acid Sequence, Animals, Chromatography, Liquid, Electrophoresis, Equipment Design, Humans, Molecular Sequence Data, Proteins, Mass Spectrometry, Proteomics
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