The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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
Keller, A., Nesvizhskii, A., Kolker, E., & Aebersold, R. (2002) · Analytical Chemistry · doi:10.1021/ac025747h · Cited by 4,970
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
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
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
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
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
Lu, P., Vogel, C., Wang, R., Yao, X., & Marcotte, E. M. (2007) · Nature Biotechnology · doi:10.1038/nbt1270 · Cited by 1,139
Desiere, F. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj040 · Cited by 910
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–421 of 421
Rossini, A. D. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.87.2018.tde-15062018-101521
Pereira, M. F. C. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.87.2019.tde-09042019-113029
Kochi, L. T. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.87.2019.tde-05042019-150733
Pareek, V., Dhayabarn, V., Balaram, H., & Krishnaswamy, P. R. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.04.412312
Eidhammer, I., Barsnes, H., Eide, G. E., & Martens, L. (2013) · Wiley eBooks · doi:10.1002/9781118494042.biblio
Dick, G. J. (2018) · Wiley eBooks · doi:10.1002/9781118708231.ch10
Wang, G. (2021) · Wiley eBooks · doi:10.1002/9780470015902.a0029240
Avaliação do papel funcional de proteínas da família HtrA de Leptospira interrogans
Daroz, B. B. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.87.2022.tde-29112022-102012
Azevedo, B. O. P. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.87.2020.tde-12092023-093250
Handunnetti, S., Silva, Y., Weerasena, J., Fernando, N., Sathkumara, H. D., Chandrapadma, N., Premawansa, S., & Rajapakse, S. (2025) · Research Square · doi:10.21203/rs.3.rs-4764619/v2
Discovery of Novel c-di-GMP-Related Genes in Leptospira interrogans
Ferrari, A. S. D. A., Merighi, D. G. S., Visnardi, A. B., Silva, G. R., Gonçalves, C. A. B., Sánchez-Limache, D. E., Ogusku, B. S. C., de Souza, A. S., de Souza, R. F., & Guzzo, C. R. (2026) · Pathogens · doi:10.3390/pathogens15020151
Rôle des phages dans l'évolution des leptospires
Schiettekatte, O. (2018) · theses.fr (ABES) · doi:10.70675/6a16452bzebb1z4de2zbde8zc54cd26f1292
Role of PerR regulators in oxidative stress response and virulence of pathogenic leptospira
Zavala-alvarado, J. C. (2019) · theses.fr (ABES) · doi:10.70675/b8f2d65fz71b5z4ec7z9fd7zea76e4a39e58
Bonhomme, D. (2022) · theses.fr (ABES) · doi:10.70675/7e306522zb260z47f1za231zdb8fb8c2d9d5
Evolutionary adaptation of pathogenic Leptospira to superoxide stress
Huete, S. G. (2024) · theses.fr (ABES) · doi:10.70675/7348c90aze74az4eb5z9de1z3462d2923e1b
Nouchikian, L. (2023) · theses.fr (ABES) · doi:10.70675/ae1b34afz3360z4758zb095z89c58db2a12f
Tillman, D. E., Durak, O., Veeraraghavan, P., Froberg, J. E., Wheeler, G. C., Budnik, B., & Macklis, J. D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.08.716720
FAIRsharing record for: Transition Markup Language
FAIRsharing Team (2015) · FAIRsharing.org · doi:10.25504/fairsharing.rz77m6
Paixao, J. E. L., Santos, F. L., Silva, I. R. M., Foltran, B. B., Gaspar, J. P., Pires, H. M., Nunes, A. B., Verdi, L. S., Stancey, M. H., Nascimento, A. L. T. O., et al. (2026) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2026.1992423
Metadata
- 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
- Health Sciences › Medicine › Infectious Diseases › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
