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Computationally unmasking each fatty acyl C=C position in complex lipids by routine LC-MS/MS lipidomics

Author

Listed:
  • Leonida M. Lamp

    (University of Graz)

  • Gosia M. Murawska

    (University of California San Diego)

  • Joseph P. Argus

    (University of California San Diego)

  • Aaron M. Armando

    (University of California San Diego)

  • Radu A. Talmazan

    (Université de Lorraine)

  • Marlene Pühringer

    (University of Vienna
    University of Vienna)

  • Evelyn Rampler

    (University of Vienna)

  • Oswald Quehenberger

    (University of California San Diego)

  • Edward A. Dennis

    (University of California San Diego
    University of California San Diego)

  • Jürgen Hartler

    (University of Graz
    University of California San Diego
    University of Graz)

Abstract

Identifying carbon-carbon double bond (C=C) positions in complex lipids is essential for elucidating physiological and pathological processes. Currently, this is impossible in high-throughput analyses of native lipids without specialized instrumentation that compromises ion yields. Here, we demonstrate automated, chain-specific identification of C=C positions in complex lipids based on the retention time derived from routine reverse-phase chromatography tandem mass spectrometry (RPLC-MS/MS). We introduce LC=CL, a computational solution that utilizes a comprehensive database capturing the elution profile of more than 2400 complex lipid species identified in RAW264.7 macrophages, including 1145 newly reported compounds. Using machine learning, LC=CL provides precise and automated C=C position assignments, adaptable to any suitable chromatographic condition. To illustrate the power of LC=CL, we re-evaluated previously published data and discovered new C=C position-dependent specificity of cytosolic phospholipase A2 (cPLA2). Accordingly, C=C position information is now readily accessible for large-scale high-throughput studies with any MS/MS instrumentation and ion activation method.

Suggested Citation

  • Leonida M. Lamp & Gosia M. Murawska & Joseph P. Argus & Aaron M. Armando & Radu A. Talmazan & Marlene Pühringer & Evelyn Rampler & Oswald Quehenberger & Edward A. Dennis & Jürgen Hartler, 2025. "Computationally unmasking each fatty acyl C=C position in complex lipids by routine LC-MS/MS lipidomics," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61911-x
    DOI: 10.1038/s41467-025-61911-x
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