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A five-level classification system for proteoform identifications

Nature Methods volume 16, pages 939–940 (2019)Cite this article

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To the Editor — The term proteoform, introduced in Nature Methods in 2013 (ref. 1), has rapidly gained acceptance in the proteomics community. The challenge and importance of comprehensively identifying proteoforms in complex samples has been recognized, and reports have begun to appear of new platforms towards that end2,3,4,5. However, one interesting central ambiguity has emerged, namely determining precisely what is meant by a ‘proteoform identification’. At present, the only practical approaches for establishing the exact primary structure of a proteoform employ mass spectrometry (MS), and a wide range of MS results claim proteoform identifications6. This seemingly small matter has significant impact, as the ambiguity in what is meant by an ‘identification’ makes it difficult to compare results from different laboratories and approaches. This situation hinders the ability of the community to evaluate technological progress and to efficiently expand biological knowledge.

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References

  1. Smith, L. M. & Kelleher, N. L. Nat. Methods 10, 186–187 (2013).

    Article  CAS  Google Scholar 

  2. Anderson, L. C. et al. J. Prot. Res. 16, 1087–1096 (2017).

    Article  CAS  Google Scholar 

  3. Lubeckyj, R. A. et al. Anal. Chem. 89, 12059–12067 (2017).

    Article  CAS  Google Scholar 

  4. Schaffer, L. V. et al. J. Prot. Res. 17, 3526–3536 (2018).

    Article  CAS  Google Scholar 

  5. Bush, D. R., Zang, L., Belov, A. M., Ivanov, A. R. & Karger, B. L. Anal. Chem. 88, 1138–1146 (2016).

    Article  CAS  Google Scholar 

  6. Lermyte, F., Tsybin, Y. O., O’Connor, P. B. & Loo, J. A. J Am. Soc. Mass. Spectrom. 30, 1149–1157 (2019).

    Article  CAS  Google Scholar 

  7. LeDuc, R. D. et al. J. Prot. Res. 13, 3231–3240 (2014).

    Article  CAS  Google Scholar 

  8. Kou, Q. et al. J. Prot. Res. 15, 2422–2432 (2016).

    Article  CAS  Google Scholar 

  9. LeDuc, R. D. et al. J. Prot. Res. 17, 1321–1325 (2018).

    Article  CAS  Google Scholar 

  10. Natale, D. A. et al. Nucleic Acids Res. 45, D339–D346 (2017).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants R35 GM126914 (to L.M.S.) and P41 GM108569 (to N.L.K.) from the NIH National Institute of General Medical Sciences, R21 LM013097 (to P.M.T.) from the National Library of Medicine, and the Sherman Fairchild Foundation (to N.L.K.).

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Authors and Affiliations

  1. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA

    Lloyd M. Smith, Michael R. Shortreed, Leah V. Schaffer & Trisha Tucholski

  2. Department of Chemistry and Molecular Biosciences, Northwestern University, Evanston, IL, USA

    Paul M. Thomas, Ryan T. Fellers, Richard D. LeDuc & Neil L. Kelleher

  3. National Resource for Translational and Developmental Proteomics, Northwestern University, Evanston, IL, USA

    Paul M. Thomas, Ryan T. Fellers, Richard D. LeDuc & Neil L. Kelleher

  4. Department of Cell and Regenerative Biology and Human Proteomics Program, University of Wisconsin-Madison, Madison, WI, USA

    Ying Ge

  5. Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA

    Jeffrey N. Agar

  6. Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Tallahassee, FL, USA

    Lissa C. Anderson

  7. Mass Spectrometry for Biology Unit, Institut Pasteur, Paris, France

    Julia Chamot-Rooke

  8. Department of Chemistry, University of Oxford, Oxford, UK

    Joseph Gault & Carol V. Robinson

  9. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA

    Joseph A. Loo

  10. Environmental Molecular Sciences Laboratory and Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA

    Ljiljana Paša-Tolić

  11. University Medical Center, Hamburg-Eppendorf, Hamburg, Germany

    Hartmut Schlüter

  12. Spectroswiss CH, Lausanne, Switzerland

    Yury O. Tsybin

  13. Institute for Research in Biomedicine, Barcelona, Spain

    Marta Vilaseca

  14. European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK

    Juan Antonio Vizcaíno

  15. Consortium for Top Down Proteomics, Cambridge, MA, USA

    Paul O. Danis

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  1. Lloyd M. Smith
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  16. Hartmut Schlüter
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  17. Yury O. Tsybin
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  20. Paul O. Danis
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  21. Neil L. Kelleher
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Corresponding authors

Correspondence to Lloyd M. Smith or Neil L. Kelleher.

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Competing interests

Y.O.T. is an employee of Spectroswiss. R.T.F., N.L.K. and R.D.L. declare a competing interest in the development and commercialization of proteoform search and management software. All other authors declare no competing interests.

Integrated supplementary information

Supplementary Figure 1 Examples of proteoform level assignments.

Different examples of proteoform identifications and the corresponding assigned level number in red.

Supplementary information

Supplementary Information

Supplementary Fig. 1 and Supplementary Table 1

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Smith, L.M., Thomas, P.M., Shortreed, M.R. et al. A five-level classification system for proteoform identifications. Nat Methods 16, 939–940 (2019). https://doi.org/10.1038/s41592-019-0573-x

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