Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans
Open accessAbstract
Mass-spectrometry-based methods for relative proteome quantification have broadly affected life science research. However, important research directions, particularly those involving mathematical modelling and simulation of biological processes, also critically depend on absolutely quantitative data--that is, knowledge of the concentration of the expressed proteins as a function of cellular state. Until now, absolute protein concentration measurements of a considerable fraction of the proteome (73%) have only been derived from genetically altered Saccharomyces cerevisiae cells, a technique that is not directly portable from yeast to other species. Here we present a mass-spectrometry-based strategy to determine the absolute quantity, that is, the average number of protein copies per cell in a cell population, for a large fraction of the proteome in genetically unperturbed cells. Applying the technology to the human pathogen Leptospira interrogans, a spirochete responsible for leptospirosis, we generated an absolute protein abundance scale for 83% of the mass-spectrometry-detectable proteome, from cells at different states. Taking advantage of the unique cellular dimensions of L. interrogans, we used cryo-electron tomography morphological measurements to verify, at the single-cell level, the average absolute abundance values of selected proteins determined by mass spectrometry on a population of cells. Because the strategy is relatively fast and applicable to any cell type, we expect that it will become a cornerstone of quantitative biology and systems biology.
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Tissue-specific amino acid precursor pools and recycling rates did not appreciably affect the results.
“Tissue-specific amino acid precursor pools and recycling rates, a pervasive problem for in vivo pulse labeling experiments 15,22 , did not appreciably affect our results (Fig. S1).”
From Global quantification of mammalian gene expression control (2011) · cites this paper as [22]
The citation is attached to the description of tissue-specific precursor pools and recycling rates as a problem for in vivo pulse labeling; the statement about 'our results' is the citing authors’ own finding. Our copy describes mass-spectrometry measurements of protein concentrations in L. interrogans (Abstract; page unavailable), but the passages found when searching for precursor pools, recycling rates, and pulse labeling do not address that problem. (LLM, conf=0.77)
Experimental — accuracy not yet measuredMass spectrometry-based methods can overcome these difficulties and were recently used to determine protein copy numbers per cell for a significant fraction of the proteome of two bacterial species and yeast.
“Mass spectrometry (MS)-based methods can overcome these difficulties and were recently used to determine protein copy numbers per cell for a significant fraction of the proteome of two bacterial species, namely Mycoplasma pneumonia and Leptospira interrogans (Malmstrom et al, 2009; Maier et al, 2011) and yeast (de Godoy et al, 2008).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
Three different protein abundance scores were calculated and their precision was validated by statistical analysis.
“We used the same data to calculate three different protein abundance scores as previously described (Ishihama et al, 2005; Silva et al, 2006; Malmstrom et al, 2009) and validated their precision by statistical analysis (Supplementary Figure S1; see Supplementary information for detail).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
The dynamic range of protein concentrations spans more than three orders of magnitude in L. interrogans and five orders of magnitude in yeast.
“We and others have previously shown that the dynamic range of protein concentrations spans more than three orders of magnitude in the bacterium L. interrogans (Malmstrom et al, 2009) and five orders of magnitude in yeast (Ghaemmaghami et al, 2003; de Godoy et al, 2008; Picotti et al, 2009).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
Those proteins make up the majority of the total protein mass and a considerable fraction of the cytoplasmic volume, while proteins functioning in signaling, protein transport, or regulatory pathways, e.g. transcription factors, comprise a minority of the quantitative proteome.
“Those proteins make up the majority of the total protein mass (Malmstrom et al, 2009) and a considerable fraction of the cytoplasmic volume (Beck et al, 2009), while proteins functioning in signaling, protein transport, or regulatory pathways, e.g. transcription factors, comprise a minority of the quantitative proteome.”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
L. interrogans expresses a relatively small number of very high copy proteins, e.g. proteins of the translation and protein folding system, metabolic enzymes as well as components of the cell wall.
“Interestingly, the bacterium L. interrogans expresses a relatively small number of in very high copy proteins, e.g. proteins of the translation and protein folding system, metabolic enzymes as well as components of the cell wall.”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
The arbitrary protein abundance indices were calibrated to absolute protein copy numbers per cell and their precision validated by bootstrapping analysis.
“The arbitrary protein abundance indices were calibrated to absolute protein copy numbers per cell their precision validated by bootstrapping analysis as described earlier (Malmstrom et al, 2009).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
The MS signal of peptides identifying each protein can be used to estimate its absolute cellular abundance.
“The MS signal of peptides identifying each protein can be used to estimate its absolute cellular abundance (de Godoy et al, 2008; Malmstrom et al, 2009; Silva et al, 2006)”
From Deep proteome and transcriptome mapping of a human cancer cell line (2011) · cites this paper as Malmstrom et al, 2009
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Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Eng, J. K., McCormack, A. L., & Yates, J. R. (1994) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(94)80016-2 · Cited by 6,484 · see citing works
Keller, A., Nesvizhskii, A., Kolker, E., & Aebersold, R. (2002) · Analytical Chemistry · doi:10.1021/ac025747h · Cited by 4,970 · see citing works
Self-citationGlobal analysis of protein expression in yeast
Ghaemmaghami, S., Huh, W.-K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., & Weissman, J. S. (2003) · Nature · doi:10.1038/nature02046 · Cited by 3,750 · see citing works
Cryo-electron microscopy of vitrified specimens
Dubochet, J., Adrian, M., Chang, J.-J., Homo, J., Lepault, J., McDowall, A. W., & Schultz, P. (1988) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500004297 · Cited by 2,397 · see citing works
Ishihama, Y., Oda, Y., Tabata, T., Sato, T., Nagasu, T., Rappsilber, J., & Mann, M. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500061-mcp200 · Cited by 2,055 · see citing works
Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS
Gerber, S. A., Rush, J., Stemman, O., Kirschner, M. W., & Gygi, S. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0832254100 · Cited by 1,733 · see citing works
Absolute Quantification of Proteins by LCMSE
Silva, J. C., Gorenstein, M. V., Li, G.-Z., Vissers, J. P. C., & Geromanos, S. J. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500230-mcp200 · Cited by 1,529 · see citing works
Lu, P., Vogel, C., Wang, R., Yao, X., & Marcotte, E. M. (2007) · Nature Biotechnology · doi:10.1038/nbt1270 · Cited by 1,139 · see citing works
Desiere, F. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj040 · Cited by 910 · see citing works
STRUCTURAL STUDIES BY ELECTRON TOMOGRAPHY: From Cells to Molecules
Lučić, V., Förster, F. G., & Baumeister, W. P. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.074112 · Cited by 703 · see citing works
Protein Mobility in the Cytoplasm of Escherichia coli
Elowitz, M. B., Surette, M. G., Wolf, P. E., Stock, J. B., & Leibler, S. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.1.197-203.1999 · Cited by 617 · see citing works
Ren, S., Fu, G., Jiang, X., Zeng, R., Miao, Y., Xu, H., Zhang, Y., Xiong, H., Lü, G., Lu, L.-F., et al. (2003) · Nature · doi:10.1038/nature01597 · Cited by 613 · see citing works
Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling
Samatey, F. A., Imada, K., Nagashima, S., Vonderviszt, F., Kumasaka, T., Yamamoto, M., & Namba, K. (2001) · Nature · doi:10.1038/35066504 · Cited by 482 · see citing works
Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli
Dwyer, D. J., Kohanski, M. A., Hayete, B., & Collins, J. J. (2007) · Molecular Systems Biology · doi:10.1038/msb4100135 · Cited by 470 · see citing works
TOM software toolbox: acquisition and analysis for electron tomography
Nickell, S., Förster, F. G., Linaroudis, A. A., Net, W. D., Beck, F., Hegerl, R., Baumeister, W. P., & Plitzko, J. M. (2004) · Journal of Structural Biology · doi:10.1016/j.jsb.2004.10.006 · Cited by 449 · see citing works
Nascimento, A. L. T. O., Ko, A. I., Martins, E. A. L., Monteiro-Vitorello, C. B., Ho, P. L., Haake, D. A., Verjovski‐Almeida, S., Hartskeerl, R. A., Marques, M. V., Oliveira, M. C., et al. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.7.2164-2172.2004 · Cited by 435 · see citing works
Snapshots of nuclear pore complexes in action captured by cryo-electron tomography
Beck, M., Lučić, V., Förster, F. G., Baumeister, W. P., & Medalia, O. (2007) · Nature · doi:10.1038/nature06170 · Cited by 349 · see citing works
Self-citationSuperHirn – a novel tool for high resolution LC‐MS‐based peptide/protein profiling
Mueller, L. N., Rinner, O., Schmidt, A., Letarte, S., Bodenmiller, B., Brusniak, M., Olga Vitek, A., Aebersold, R. H., & Müller, M. (2007) · PROTEOMICS · doi:10.1002/pmic.200700057 · Cited by 308 · see citing works
Self-citationGenetics of Motility and Chemotaxis of a Fascinating Group of Bacteria: The Spirochetes
Charon, N. W., & Goldstein, S. F. (2002) · Annual Review of Genetics · doi:10.1146/annurev.genet.36.041602.134359 · Cited by 304 · see citing works
Lange, V., Malmström, J. A., Didion, J. P., King, N. L., Johansson, B. P., Schäfer, J., Rameseder, J., Wong, C., Deutsch, E. W., Brusniak, M., et al. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800032-mcp200 · Cited by 203 · see citing works
Self-citationStoichiometric analysis of the flagellar hook-(basal-body) complex of Salmonella typhimurium
Jones, C. J., Macnab, R. M., Okino, H., & Aizawa, S.-I. (1990) · Journal of Molecular Biology · doi:10.1016/0022-2836(90)90132-6 · Cited by 170 · see citing works
The EM Program Package: A Platform for Image Processing in Biological Electron Microscopy
Hegerl, R. (1996) · Journal of Structural Biology · doi:10.1006/jsbi.1996.0006 · Cited by 159 · see citing works
Schmidt, A., Gehlenborg, N., Bodenmiller, B., Mueller, L. N., Campbell, D., Mueller, M., Aebersold, R. H., & Domon, B. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700498-mcp200 · Cited by 140 · see citing works
Self-citationChanges in the surface of Leptospira interrogans serovar grippotyphosa during in vitro cultivation
Haake, D. A., Walker, E. M., Blanco, D. R., Bolin, C. A., Miller, M. N., & Lovett, M. (1991) · Infection and Immunity · doi:10.1128/iai.59.3.1131-1140.1991 · Cited by 127 · see citing works
Location and architecture of the Caulobacter crescentus chemoreceptor array
Briegel, A., Ding, H. J., Li, Z., Werner, J., Gitai, Z., Dias, D. P., Jensen, R. B., & Jensen, G. J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06219.x · Cited by 113 · see citing works
Heller, M., Ye, M., Michel, P. E., Morier, P., Stalder, D., Jünger, M. A., Aebersold, R. H., Reymond, F., & Rossier, J. S. (2005) · Journal of Proteome Research · doi:10.1021/pr050193v · Cited by 101 · see citing works
Self-citationYi, E. C., Lee, H., Aebersold, R. H., & Goodlett, D. R. (2003) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1150 · Cited by 97 · see citing works
Self-citationMalmström, J. A., Lee, H., Nesvizhskii, A. I., Shteynberg, D. D., Mohanty, S., Brunner, E., Ye, M., Weber, G., Eckerskorn, C., & Aebersold, R. H. (2006) · Journal of Proteome Research · doi:10.1021/pr0600632 · Cited by 89 · see citing works
Self-citationVogel, C., & Marcotte, E. M. (2008) · Nature Protocols · doi:10.1038/nprot.2008.132 · Cited by 85 · see citing works
Sosinsky, G. E., Francis, N. R., DeRosier, D. J., Wall, J. S., Simon, M. N., & Hainfeld, J. F. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.11.4801 · Cited by 59 · see citing works
Efficacy of ciprofloxacin against Leptospira interrogans serogroup icterohaemorrhagiae
Shalit, I., Barnea, A. R., & Shahar, A. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.5.788 · Cited by 31 · see citing works
Reckinger, A. R., Jeong, K. S., Khodursky, A. B., & Hiasa, H. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl981 · Cited by 21 · see citing works
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Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195 · see citing works
On the Dependency of Cellular Protein Levels on mRNA Abundance
Liu, Y., Beyer, A., & Aebersold, R. (2016) · Cell · doi:10.1016/j.cell.2016.03.014 · Cited by 3,221 · 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
Self-citationCorrelation of mRNA and protein in complex biological samples
Maier, T., Güell, M., & Serrano, L. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.10.036 · Cited by 1,802 · see citing works
Protein 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
Deep proteome and transcriptome mapping of a human cancer cell line
Nagaraj, N., Wisniewski, J. R., Geiger, T., Cox, J., Kircher, M., Kelso, J., Pääbo, S., & Mann, M. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.81 · Cited by 979 · see citing works
The quantitative proteome of a human cell line
Beck, M., Schmidt, A., Malmstroem, J., Claassen, M., Ori, A., Szymborska, A., Herzog, F., Rinner, O., Ellenberg, J., & Aebersold, R. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.82 · Cited by 816 · see citing works
Self-citationQuantitative mass spectrometry in proteomics: critical review update from 2007 to the present
Bantscheff, M., Lemeer, S., Savitski, M. M., & Kuster, B. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-6203-4 · Cited by 801 · see citing works
Geiger, T., Wehner, A., Schaab, C., Cox, J., & Mann, M. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.014050 · Cited by 797 · see citing works
The quantitative and condition-dependent Escherichia coli proteome
Schmidt, A., Kochanowski, K., Vedelaar, S. R., Ahrné, E., Volkmer, B., Callipo, L., Knoops, K., Bauer, M., Aebersold, R. H., & Heinemann, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3418 · Cited by 737 · see citing works
Self-citationLess label, more free: Approaches in label‐free quantitative mass spectrometry
Neilson, K. A., Ali, N., Muralidharan, S., Mirzaei, M., Mariani, M., Assadourian, G., Lee, A., Sluyter, S. C. V., & Haynes, P. A. (2011) · PROTEOMICS · doi:10.1002/pmic.201000553 · Cited by 701 · see citing works
A “Proteomic Ruler” for Protein Copy Number and Concentration Estimation without Spike-in Standards
Wiśniewski, J. R., Hein, M. Y., Cox, J., & Mann, M. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.037309 · Cited by 690 · see citing works
Quantitative, High-Resolution Proteomics for Data-Driven Systems Biology
Cox, J., & Mann, M. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061308-093216 · Cited by 685 · see citing works
Options and considerations when selecting a quantitative proteomics strategy
Domon, B., & Aebersold, R. H. (2010) · Nature Biotechnology · doi:10.1038/nbt.1661 · Cited by 601 · see citing works
Self-citationTranslation efficiency is determined by both codon bias and folding energy
Tuller, T., Waldman, Y. Y., Kupiec, M., & Ruppin, E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909910107 · Cited by 584 · see citing works
Decoding signalling networks by mass spectrometry-based proteomics
Choudhary, C., & Mann, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2900 · Cited by 575 · see citing works
Shteynberg, D. D., Deutsch, E. W., Lam, H., Eng, J. K., Sun, Z., Tasman, N., Mendoza, L., Moritz, R. L., Aebersold, R. H., & Nesvizhskii, A. I. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.007690 · Cited by 548 · see citing works
Self-citationLundby, A., Lage, K., Weinert, B. T., Bekker‐Jensen, D. B., Secher, A., Skovgaard, T., Kelstrup, C. D., Dmytriyev, A., Choudhary, C., Lundby, C., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.07.006 · Cited by 544 · see citing works
Mass spectrometry in high-throughput proteomics: ready for the big time
Nilsson, T., Mann, M., Aebersold, R., Yates, J. R., Bairoch, A., & Bergeron, J. J. M. (2010) · Nature Methods · doi:10.1038/nmeth0910-681 · Cited by 470 · see citing works
Self-citationPaxdb, a database of protein abundance averages across all three domains of life
Wang, M., Weiss, M., Simonovic, M., Haertinger, G., Schrimpf, S. P., Hengartner, M. O., & von Mering, C. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o111.014704 · Cited by 466 · see citing works
Fraga, T. R., Carvalho, E., Isaac, L., & Barbosa, A. S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397169-2.00107-4 · Cited by 457 · see citing works
Virulence of the zoonotic agent of leptospirosis: still terra incognita?
Picardeau, M. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.5 · Cited by 413 · see citing works
Mass spectrometry–based proteomics in cell biology
Walther, T. C., & Mann, M. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201004052 · Cited by 411 · see citing works
Mass Spectrometry–Based Proteomics and Network Biology
Bensimon, A., Heck, A. J. R., & Aebersold, R. H. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-072909-100424 · Cited by 407 · see citing works
Self-citationDepletion of Abundant Plasma Proteins and Limitations of Plasma Proteomics
Tu, C., Rudnick, P. A., Martinez, M. Y., Cheek, K. L., Stein, S. E., Slebos, R. J. C., & Liebler, D. C. (2010) · Journal of Proteome Research · doi:10.1021/pr100646w · Cited by 390 · see citing works
Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria
Hui, S., Silverman, J. M., Chen, S. S., Erickson, D. W., Basan, M., Wang, J., Hwa, T., & Williamson, J. R. (2015) · Molecular Systems Biology · doi:10.15252/msb.20145697 · Cited by 369 · see citing works
Next-generation synthetic gene networks
Lu, T. K., Khalil, A. S., & Collins, J. J. (2009) · Nature Biotechnology · doi:10.1038/nbt.1591 · Cited by 365 · see citing works
Leptospira as an Emerging Pathogen: A Review of its Biology, Pathogenesis and Host Immune Responses
Evangelista, K. V., & Coburn, J. (2010) · Future Microbiology · doi:10.2217/fmb.10.102 · Cited by 354 · see citing works
The Coming Age of Complete, Accurate, and Ubiquitous Proteomes
Mann, M., Kulak, N. A., Nagaraj, N., & Cox, J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.029 · Cited by 350 · see citing works
Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues
Lundby, A., Secher, A., Lage, K., Nordsborg, N. B., Dmytriyev, A., Lundby, C., & Olsen, J. V. (2012) · Nature Communications · doi:10.1038/ncomms1871 · Cited by 341 · see citing works
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Beck, M., & Baumeister, W. P. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.08.006 · Cited by 313 · see citing works
Self-citationWhat Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira
Fouts, D. E., Matthias, M. A., Adhikarla, H., Adler, B., Santos, L. A., Berg, D. E., Bulach, D., Buschiazzo, A., Chang, Y.-F., Galloway, R. L., et al. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004403 · Cited by 311 · see citing works
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Gholami, A. M., Hahne, H., Wu, Z., Auer, F. J., Meng, C., Wilhelm, M., & Kuster, B. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.018 · Cited by 302 · see citing works
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Maier, T., Schmidt, A., Güell, M., Kühner, S., Gavin, A., Aebersold, R., & Serrano, L. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.38 · Cited by 297 · see citing works
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Iijima, T., Wu, K., Witte, H., Hanno-Iijima, Y., Glatter, T., Richard, S., & Scheiffele, P. (2011) · Cell · doi:10.1016/j.cell.2011.11.028 · Cited by 279 · see citing works
Proteomics on an Orbitrap Benchtop Mass Spectrometer Using All-ion Fragmentation
Geiger, T., Cox, J., & Mann, M. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.001537 · Cited by 253 · see citing works
Chemical Analysis of Single Cells
Lin, Y., Trouillon, R., Рустамовна, С. Г., & Ewing, A. G. (2011) · Analytical Chemistry · doi:10.1021/ac2009838 · Cited by 251 · see citing works
Quantitative Analysis of the Intra- and Inter-Individual Variability of the Normal Urinary Proteome
Nagaraj, N., & Mann, M. (2010) · Journal of Proteome Research · doi:10.1021/pr100835s · Cited by 248 · see citing works
Critical assessment of proteome‐wide label‐free absolute abundance estimation strategies
Ahrné, E., Molzahn, L., Glatter, T., & Schmidt, A. (2013) · PROTEOMICS · doi:10.1002/pmic.201300135 · Cited by 247 · see citing works
Self-citationPhenotypic bistability in Escherichia coli's central carbon metabolism
Kotte, O., Volkmer, B., Radzikowski, J. L., & Heinemann, M. (2014) · Molecular Systems Biology · doi:10.15252/msb.20135022 · Cited by 242 · see citing works
Quaternary dynamics and plasticity underlie small heat shock protein chaperone function
Stengel, F., Baldwin, A. J., Painter, A. J., Jaya, N., Basha, E., Kay, L. E., Vierling, E., Robinson, C. V., & Benesch, J. L. P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910126107 · Cited by 242 · see citing works
Saito, M. A., Bertrand, E. M., Dutkiewicz, S., Bulygin, V. V., Moran, D. M., Monteiro, F., Follows, M. J., Valois, F. W., & Waterbury, J. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006943108 · Cited by 241 · see citing works
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Cheng, A. A., & Lu, T. K. (2012) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071811-150118 · Cited by 241 · see citing works
Proteome of mouse oocytes at different developmental stages
Wang, S., Kou, Z., Jing, Z., Zhang, Y., Guo, X., Dong, M., Wilmut, I., & Gao, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013185107 · Cited by 239 · see citing works
Protein 19 F NMR in Escherichia coli
Li, C., Wang, G.-F., Wang, Y., Creager-Allen, R. L., Lutz, E. A., Scronce, H., Slade, K. M., Ruf, R. A. S., Mehl, R. A., & Pielak, G. J. (2009) · Journal of the American Chemical Society · doi:10.1021/ja907966n · Cited by 226 · see citing works
Shi, T., Fillmore, T., Sun, X., Zhao, R., Schepmoes, A., Hossain, M., Xie, F., Wu, S., Kim, J., Jones, N., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1204366109 · Cited by 220 · see citing works
Multiple nutrient stresses at intersecting Pacific Ocean biomes detected by protein biomarkers
Saito, M. A., McIlvin, M. R., Moran, D. M., Goepfert, T. J., DiTullio, G. R., Post, A. F., & Lamborg, C. H. (2014) · Science · doi:10.1126/science.1256450 · Cited by 217 · see citing works
Rapid tests for diagnosis of leptospirosis: Current tools and emerging technologies
Picardeau, M., Bertherat, E., Jancloes, M., nikolaos, S. A., Durski, K. N., & Hartskeerl, R. A. (2013) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2013.09.012 · Cited by 203 · see citing works
Schubert, O. T., Mouritsen, J., Ludwig, C., Röst, H. L., Rosenberger, G., Arthur, P. K., Claassen, M., Campbell, D. S., Sun, Z., Farrah, T., et al. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.04.008 · Cited by 173 · see citing works
Self-citationGenerating and navigating proteome maps using mass spectrometry
Ahrens, C. H., Brunner, E., Qeli, E., Basler, K., & Aebersold, R. H. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2973 · Cited by 167 · see citing works
Self-citationArike, L., Valgepea, K., Peil, L., Nahku, R., Adamberg, K., & Vilu, R. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.06.020 · Cited by 167 · see citing works
An automated pipeline for high-throughput label-free quantitative proteomics
Weisser, H., Nahnsen, S., Grossmann, J., Nilse, L., Quandt, A., Brauer, H., Sturm, M., Kenar, E., Kohlbacher, O., Aebersold, R., et al. (2013) · Journal of Proteome Research · doi:10.1021/pr300992u · Cited by 160 · see citing works
Self-citationVisual proteomics of the human pathogen Leptospira interrogans
Beck, M., Malmström, J. A., Lange, V., Schmidt, A., Deutsch, E. W., & Aebersold, R. (2009) · Nature Methods · doi:10.1038/nmeth.1390 · Cited by 156 · see citing works
Self-citationIdentifier mapping performance for integrating transcriptomics and proteomics experimental results
Day, R., McDade, K. K., Chandran, U. R., Lisovich, A., Conrads, T. P., Hood, B. L., Kolli, V. S. K., Kirchner, D. R., Litzi, T., & Maxwell, G. L. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-213 · Cited by 155 · see citing works
Fraga, T. R., Carvalho, E., Isaac, L., & Barbosa, A. S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-818619-0.00159-3 · Cited by 155 · see citing works
Lambert, A., Picardeau, M., Haake, D. A., Sermswan, R. W., Srikram, A., Adler, B., & Murray, G. L. (2012) · Infection and Immunity · doi:10.1128/iai.00131-12 · Cited by 146 · see citing works
Small Heat-Shock Proteins: Paramedics of the Cell
Hilton, G. R., Lioe, H., Stengel, F., Baldwin, A. J., & Benesch, J. L. P. (2012) · Topics in current chemistry · doi:10.1007/128_2012_324 · Cited by 144 · see citing works
Standardization approaches in absolute quantitative proteomics with mass spectrometry
Calderón‐Celis, F., Encinar, J. R., & Sanz‐Medel, A. (2017) · Mass Spectrometry Reviews · doi:10.1002/mas.21542 · Cited by 141 · see citing works
Ludwig, C., Claassen, M., Schmidt, A., & Aebersold, R. H. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.013987 · Cited by 137 · see citing works
Self-citationLiu, L., Yu, M., Zhang, Y., Wang, C., & Lu, H. (2014) · ACS Applied Materials & Interfaces · doi:10.1021/am501110e · Cited by 135 · see citing works
Chavez, J. D., Lee, C. F., Caudal, A., Keller, A., Tian, R., & Bruce, J. E. (2017) · Cell Systems · doi:10.1016/j.cels.2017.10.017 · Cited by 135 · see citing works
Quantitative dissection of the simple repression input–output function
García, H. G., & Phillips, R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015616108 · Cited by 127 · see citing works
Eyers, C. E., Lawless, C., Wedge, D. C., Lau, K. W., Gaskell, S. J., & Hubbard, S. J. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.003384 · Cited by 126 · see citing works
Application of targeted mass spectrometry in bottom-up proteomics for systems biology research
Manes, N. P., & Nita‐Lazar, A. (2018) · Journal of Proteomics · doi:10.1016/j.jprot.2018.02.008 · Cited by 124 · see citing works
Scheres, S. H. W., Melero, R., Valle, M., & Carazo, J. M. (2009) · Structure · doi:10.1016/j.str.2009.10.009 · Cited by 117 · see citing works
Computational methods for electron tomography
Fernández, J. (2012) · Micron · doi:10.1016/j.micron.2012.05.003 · Cited by 117 · see citing works
Kraeutler, M. J., Soltis, A. R., & Saucerman, J. J. (2010) · BMC Systems Biology · doi:10.1186/1752-0509-4-157 · Cited by 113 · see citing works
Izard, J., Renken, C. W., Hsieh, C., Desrosiers, D. C., Dunham-Ems, S. M., Vake, C. J. L., Gebhardt, L. L., Limberger, R. J., Cox, D. L., Marko, M., et al. (2009) · Journal of Bacteriology · doi:10.1128/jb.01031-09 · Cited by 111 · see citing works
Mass spectrometry-based proteomics for systems biology
Sabidó, E., Selevsek, N., & Aebersold, R. H. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2011.11.014 · Cited by 108 · see citing works
Self-citationGoeminne, L. J. E., Gevaert, K., & Clement, L. (2017) · Journal of Proteomics · doi:10.1016/j.jprot.2017.04.004 · Cited by 106 · see citing works
Absolute quantification of microbial proteomes at different states by directed mass spectrometry
Schmidt, A., Beck, M., Malmström, J. A., Lam, H., Claassen, M., Campbell, D. S., & Aebersold, R. H. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.37 · Cited by 101 · see citing works
Self-citationMalmström, E., Kilsgård, O., Hauri, S., Smeds, E., Herwald, H., Malmström, L., & Malmström, J. A. (2016) · Nature Communications · doi:10.1038/ncomms10261 · Cited by 101 · see citing works
Self-citationFarley, M. M., Hu, B., Margolin, W., & Liu, J. (2016) · Journal of Bacteriology · doi:10.1128/jb.00901-15 · Cited by 101 · see citing works
Evolutionary meandering of intermolecular interactions along the drift barrier
Lynch, M., & Hagner, K. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421641112 · Cited by 100 · see citing works
TraML—A Standard Format for Exchange of Selected Reaction Monitoring Transition Lists
Deutsch, E. W., Chambers, M., Neumann, S., Levander, F., Binz, P., Shofstahl, J., Campbell, D. S., Mendoza, L., Ovelleiro, D., Helsens, K., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r111.015040 · Cited by 100 · see citing works
Self-citationHigh Precision Platelet Releasate Definition by Quantitative Reversed Protein Profiling—Brief Report
Wijten, P., van Holten, T. C., Woo, L. L., Bleijerveld, O. B., Roest, M., Heck, A. J. R., & Scholten, A. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301147 · Cited by 100 · see citing works
Leptospira interrogans Catalase Is Required for Resistance to H 2 O 2 and for Virulence
Eshghi, A., Lourdault, K., Murray, G. L., Bartpho, T., Sermswan, R. W., Picardeau, M., Adler, B., Snarr, B. D., Zuerner, R. L., & Cameron, C. E. (2012) · Infection and Immunity · doi:10.1128/iai.00466-12 · Cited by 98 · see citing works
OmpL1 Is an Extracellular Matrix- and Plasminogen-Interacting Protein of Leptospira spp
Fernandes, L. G. V., Vieira, M. L., Kirchgatter, K., Alves, I. J., de Morais, Z. M., Vasconcellos, S. A., Romero, E. C., & Nascimento, A. L. T. O. (2012) · Infection and Immunity · doi:10.1128/iai.00474-12 · Cited by 98 · see citing works
A new view into prokaryotic cell biology from electron cryotomography
Oikonomou, C. M., Chang, Y., & Jensen, G. J. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.7 · Cited by 97 · see citing works
Motility Is Crucial for the Infectious Life Cycle of Borrelia burgdorferi
Sultan, S. Z., Manne, A., Stewart, P. E., Bestor, A. C., Rosa, P. A., Charon, N. W., & Motaleb, M. A. (2013) · Infection and Immunity · doi:10.1128/iai.01228-12 · Cited by 96 · see citing works
Muntel, J., Fromion, V., Goelzer, A., Maaß, S., Mäder, U., Büttner, K., Hecker, M., & Becher, D. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.032631 · Cited by 95 · see citing works
Wu, Q., Yuan, H., Zhang, L., & Zhang, Y. (2012) · Analytica Chimica Acta · doi:10.1016/j.aca.2012.04.010 · Cited by 94 · see citing works
Directed mass spectrometry: towards hypothesis-driven proteomics
Schmidt, A., Claassen, M., & Aebersold, R. H. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.08.016 · Cited by 92 · see citing works
Self-citationOliveira, R., de Morais, Z. M., Gonçales, A. P., Romero, E. C., Vasconcellos, S. A., & Nascimento, A. L. T. O. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021962 · Cited by 91 · see citing works
Xue, F., Dong, H., Wu, J., Wu, Z., Hu, W., Sun, A., Troxell, B., Yang, X., & Yan, J. (2010) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000857 · Cited by 91 · see citing works
Protease bias in absolute protein quantitation
Peng, M., Taouatas, N., Cappadona, S., van Breukelen, B., Mohammed, S., Scholten, A., & Heck, A. J. R. (2012) · Nature Methods · doi:10.1038/nmeth.2031 · Cited by 90 · see citing works
Pinne, M., Choy, H. A., & Haake, D. A. (2010) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000815 · Cited by 90 · see citing works
Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring
Lawless, C., Holman, S. W., Brownridge, P., Lanthaler, K., Harman, V. M., Watkins, R. H., Hammond, D. E., Miller, R. L., Sims, P. F. G., Grant, C. M., et al. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.054288 · Cited by 87 · see citing works
Wunder, E. A., Figueira, C. P., Benaroudj, N., Hu, B., Tong, B. A., Trajtenberg, F., Liu, J., dos Reis, M. G., Charon, N. W., Buschiazzo, A., et al. (2016) · Molecular Microbiology · doi:10.1111/mmi.13403 · Cited by 87 · see citing works
The Molecular Basis of Leptospiral Pathogenesis
Murray, G. L. (2014) · Current topics in microbiology and immunology · doi:10.1007/978-3-662-45059-8_7 · Cited by 86 · see citing works
The lipoprotein LipL32, an enigma of leptospiral biology
Murray, G. L. (2012) · Veterinary Microbiology · doi:10.1016/j.vetmic.2012.11.005 · Cited by 86 · see citing works
The Proteome of Cholesteryl-Ester-Enriched Versus Triacylglycerol-Enriched Lipid Droplets
Khor, V. K., Ahrends, R., Lin, Y., Shen, W., Adams, C. M., Roseman, A. N., Cortez, Y., Teruel, M. N., Azhar, S., & Kraemer, F. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105047 · Cited by 86 · see citing works
Pinne, M., & Haake, D. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0051025 · Cited by 85 · see citing works
Classic reaction kinetics can explain complex patterns of antibiotic action
Wiesch, P. A. Z., Abel, S., Gkotzis, S., Ocampo, P., Engelstädter, J., Hinkley, T., Magnus, C., Waldor, M. K., Udekwu, K. I., & Cohen, T. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa8760 · Cited by 85 · see citing works
Raddi, G., Morado, D. R., Yan, J., Haake, D. A., Yang, X., & Liu, J. (2012) · Journal of Bacteriology · doi:10.1128/jb.06474-11 · Cited by 84 · see citing works
Beck, M., Claassen, M., & Aebersold, R. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2010.09.002 · Cited by 83 · see citing works
Self-citationSouza, N. M., Vieira, M. L., Alves, I. J., de Morais, Z. M., Vasconcellos, S. A., & Nascimento, A. L. T. O. (2012) · Microbial Pathogenesis · doi:10.1016/j.micpath.2012.06.001 · Cited by 80 · see citing works
- Authors
- Malmström, J., Beck, M., Schmidt, A., Lange, V., Deutsch, E. W., & Aebersold, R.
- Affiliations
- ETH Zurich (CH)
- Institute for Systems Biology (US)
- University of Zurich (CH)
- Corresponding author
- Aebersold, Ruedi
- Venue
- Nature
- Published
- 2009-07-15
- Volume
- 460
- Issue
- 7256
- Pages
- 762-765
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2723184
- OpenAlex
- W2041852635
- Cited by
- 421
- References
- 33
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 17 · 2019: 17 · 2018: 28 · 2017: 20 · 2016: 28 · 2015: 23 · 2014: 35 · 2013: 37 · 2012: 60
- FWCI
- 23.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (n01hv28179-12-0-0)
- National Heart, Lung, and Blood Institute (N01 HV028179, N01-HV-28179)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Immunology and Microbiology › Parasitology › Leptospirosis research and findings
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- Leptospira interrogans, protein copy number, leptospirosis, cryo-electron tomography, quantitative proteomics, spirochetes
- MeSH terms
- Bacterial Proteins, Chromatography, High Pressure Liquid, Chromatography, Liquid, Humans, Leptospira interrogans, Mass Spectrometry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cryoelectron Microscopy, Proteome, Proteomics, Tandem Mass Spectrometry, Electron Microscope Tomography
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