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Title: Best practices and benchmarks for intact protein analysis for top-down mass spectrometry

Abstract

One gene can give rise to many functionally distinct proteoforms, each of which has a characteristic molecular mass. Top-down mass spectrometry enables the analysis of intact proteins and proteoforms. Here members of the Consortium for Top-Down Proteomics provide a decision tree that guides researchers to robust protocols for mass analysis of intact proteins (antibodies, membrane proteins and others) from mixtures of varying complexity. We also present cross-platform analytical benchmarks using a protein standard sample, to allow users to gauge their proficiency.

Authors:
ORCiD logo [1];  [1];  [2];  [2]; ORCiD logo [2];  [3]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [6]; ORCiD logo [3];  [7];  [7];  [1];  [1];  [8]; ORCiD logo [4]; ORCiD logo [9];  [1]; ORCiD logo [7]; ORCiD logo [10] more »; ORCiD logo [11];  [12];  [3]; ORCiD logo [13]; ORCiD logo [7]; ORCiD logo [3]; ORCiD logo [2]; ORCiD logo [1] « less
  1. Northeastern Univ., Boston, MA (United States)
  2. Northwestern Univ., Evanston, IL (United States)
  3. Univ. of Wisconsin-Madison, Madison, WI (United States)
  4. Discovery Attribute Sciences, Thousand Oaks, CA (United States)
  5. Northeastern Univ., Boston, MA (United States); Alnylam Pharmaceuticals, Cambridge, MA (United States)
  6. Northeastern Univ., Boston, MA (United States); Biogen, Cambridge, MA (United States)
  7. Univ. of California, Los Angeles, CA (United States)
  8. Bruker Daltonics, Billerica, MA (United States)
  9. Northeastern Univ., Burlington, MA (United States)
  10. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  11. Institut Pasteur, Paris (France)
  12. Eastwoods Consulting, Boylston, MA (United States)
  13. Spectroswiss, Lausanne (Switzerland)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1542102
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Nature Methods
Additional Journal Information:
Journal Volume: 16; Journal Issue: 7; Journal ID: ISSN 1548-7091
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

Citation Formats

Donnelly, Daniel P., Rawlins, Catherine M., DeHart, Caroline J., Fornelli, Luca, Schachner, Luis F., Lin, Ziqing, Lippens, Jennifer L., Aluri, Krishna C., Sarin, Richa, Chen, Bifan, Lantz, Carter, Jung, Wonhyeuk, Johnson, Kendall R., Koller, Antonius, Wolff, Jeremy J., Campuzano, Iain D. G., Auclair, Jared R., Ivanov, Alexander R., Whitelegge, Julian P., Paša-Tolić, Ljiljana, Chamot-Rooke, Julia, Danis, Paul O., Smith, Lloyd M., Tsybin, Yury O., Loo, Joseph A., Ge, Ying, Kelleher, Neil L., and Agar, Jeffrey N. Best practices and benchmarks for intact protein analysis for top-down mass spectrometry. United States: N. p., 2019. Web. doi:10.1038/S41592-019-0457-0.
Donnelly, Daniel P., Rawlins, Catherine M., DeHart, Caroline J., Fornelli, Luca, Schachner, Luis F., Lin, Ziqing, Lippens, Jennifer L., Aluri, Krishna C., Sarin, Richa, Chen, Bifan, Lantz, Carter, Jung, Wonhyeuk, Johnson, Kendall R., Koller, Antonius, Wolff, Jeremy J., Campuzano, Iain D. G., Auclair, Jared R., Ivanov, Alexander R., Whitelegge, Julian P., Paša-Tolić, Ljiljana, Chamot-Rooke, Julia, Danis, Paul O., Smith, Lloyd M., Tsybin, Yury O., Loo, Joseph A., Ge, Ying, Kelleher, Neil L., & Agar, Jeffrey N. Best practices and benchmarks for intact protein analysis for top-down mass spectrometry. United States. doi:10.1038/S41592-019-0457-0.
Donnelly, Daniel P., Rawlins, Catherine M., DeHart, Caroline J., Fornelli, Luca, Schachner, Luis F., Lin, Ziqing, Lippens, Jennifer L., Aluri, Krishna C., Sarin, Richa, Chen, Bifan, Lantz, Carter, Jung, Wonhyeuk, Johnson, Kendall R., Koller, Antonius, Wolff, Jeremy J., Campuzano, Iain D. G., Auclair, Jared R., Ivanov, Alexander R., Whitelegge, Julian P., Paša-Tolić, Ljiljana, Chamot-Rooke, Julia, Danis, Paul O., Smith, Lloyd M., Tsybin, Yury O., Loo, Joseph A., Ge, Ying, Kelleher, Neil L., and Agar, Jeffrey N. Thu . "Best practices and benchmarks for intact protein analysis for top-down mass spectrometry". United States. doi:10.1038/S41592-019-0457-0. https://www.osti.gov/servlets/purl/1542102.
@article{osti_1542102,
title = {Best practices and benchmarks for intact protein analysis for top-down mass spectrometry},
author = {Donnelly, Daniel P. and Rawlins, Catherine M. and DeHart, Caroline J. and Fornelli, Luca and Schachner, Luis F. and Lin, Ziqing and Lippens, Jennifer L. and Aluri, Krishna C. and Sarin, Richa and Chen, Bifan and Lantz, Carter and Jung, Wonhyeuk and Johnson, Kendall R. and Koller, Antonius and Wolff, Jeremy J. and Campuzano, Iain D. G. and Auclair, Jared R. and Ivanov, Alexander R. and Whitelegge, Julian P. and Paša-Tolić, Ljiljana and Chamot-Rooke, Julia and Danis, Paul O. and Smith, Lloyd M. and Tsybin, Yury O. and Loo, Joseph A. and Ge, Ying and Kelleher, Neil L. and Agar, Jeffrey N.},
abstractNote = {One gene can give rise to many functionally distinct proteoforms, each of which has a characteristic molecular mass. Top-down mass spectrometry enables the analysis of intact proteins and proteoforms. Here members of the Consortium for Top-Down Proteomics provide a decision tree that guides researchers to robust protocols for mass analysis of intact proteins (antibodies, membrane proteins and others) from mixtures of varying complexity. We also present cross-platform analytical benchmarks using a protein standard sample, to allow users to gauge their proficiency.},
doi = {10.1038/S41592-019-0457-0},
journal = {Nature Methods},
number = 7,
volume = 16,
place = {United States},
year = {2019},
month = {6}
}

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