IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46610-3.html
   My bibliography  Save this article

Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology

Author

Listed:
  • Frantisek Filandr

    (University of Calgary)

  • Vladimir Sarpe

    (University of Calgary)

  • Shaunak Raval

    (University of Calgary
    University of Calgary)

  • D. Alex Crowder

    (University of Calgary)

  • Morgan F. Khan

    (University of Calgary)

  • Pauline Douglas

    (University of Calgary)

  • Stephen Coales

    (Trajan Scientific & Medical - Raleigh)

  • Rosa Viner

    (Thermo Fisher Scientific)

  • Aleem Syed

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • John A. Tainer

    (The University of Texas MD Anderson Cancer Center
    Lawrence Berkeley National Laboratory)

  • Susan P. Lees-Miller

    (University of Calgary)

  • David C. Schriemer

    (University of Calgary
    University of Calgary)

Abstract

We present a hydrogen/deuterium exchange workflow coupled to tandem mass spectrometry (HX-MS2) that supports the acquisition of peptide fragment ions alongside their peptide precursors. The approach enables true auto-curation of HX data by mining a rich set of deuterated fragments, generated by collisional-induced dissociation (CID), to simultaneously confirm the peptide ID and authenticate MS1-based deuteration calculations. The high redundancy provided by the fragments supports a confidence assessment of deuterium calculations using a combinatorial strategy. The approach requires data-independent acquisition (DIA) methods that are available on most MS platforms, making the switch to HX-MS2 straightforward. Importantly, we find that HX-DIA enables a proteomics-grade approach and wide-spread applications. Considerable time is saved through auto-curation and complex samples can now be characterized and at higher throughput. We illustrate these advantages in a drug binding analysis of the ultra-large protein kinase DNA-PKcs, isolated directly from mammalian cells.

Suggested Citation

  • Frantisek Filandr & Vladimir Sarpe & Shaunak Raval & D. Alex Crowder & Morgan F. Khan & Pauline Douglas & Stephen Coales & Rosa Viner & Aleem Syed & John A. Tainer & Susan P. Lees-Miller & David C. Sc, 2024. "Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46610-3
    DOI: 10.1038/s41467-024-46610-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46610-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46610-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Shikang Liang & Sherine E. Thomas & Amanda K. Chaplin & Steven W. Hardwick & Dimitri Y. Chirgadze & Tom L. Blundell, 2022. "Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs," Nature, Nature, vol. 601(7894), pages 643-648, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Metztli Cisneros-Aguirre & Felicia Wednesday Lopezcolorado & Linda Jillianne Tsai & Ragini Bhargava & Jeremy M. Stark, 2022. "The importance of DNAPKcs for blunt DNA end joining is magnified when XLF is weakened," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46610-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.