Introduction

Untargeted omics analyses aim to comprehensively characterize biomolecules within a biological system. Changes in the presence or quantity of these biomolecules can indicate important biological perturbations, such as those caused by disease. With current technological advancements, the entire genome can now be sequenced; however, in the burgeoning fields of lipidomics, only a subset of lipids can be identified. The recent emergence of high resolution tandem mass spectrometry (HR-MS/MS), in combination with ultra-high performance liquid chromatography, has resulted in an increased coverage of the lipidome. Nevertheless, identifications from MS/MS are generally limited by the number of precursors that can be selected for fragmentation during chromatographic elution. Therefore, we developed the software IE-Omics to automate iterative exclusion (IE), where selected precursors using data-dependent topN analyses are excluded in sequential injections. In each sequential injection, unique precursors are fragmented until HR-MS/MS spectra of all ions above a user-defined intensity threshold are acquired. IE-Omics was applied to lipidomic analyses in Red Cross plasma and substantia nigra tissue. Coverage of the lipidome was drastically improved using IE. When applying IE-Omics to Red Cross plasma and substantia nigra lipid extracts in positive ion mode, 69% and 40% more molecular identifications were obtained, respectively. In addition, applying IE-Omics to a lipidomics workflow increased the coverage of trace species, including odd-chained and short-chained diacylglycerides and oxidized lipid species. By increasing the coverage of the lipidome, applying IE to a lipidomics workflow increases the probability of finding biomarkers and provides additional information for determining etiology of disease. Graphical Abstract ᅟ.

Publications

  1. Expanding Lipidome Coverage Using LC-MS/MS Data-Dependent Acquisition with Automated Exclusion List Generation.
    Cite this
    Koelmel JP, Kroeger NM, Gill EL, Ulmer CZ, Bowden JA, Patterson RE, Yost RA, Garrett TJ, 2017-05-01 - Journal of the American Society for Mass Spectrometry

Credits

  1. Jeremy P Koelmel
    Developer

    Department of Chemistry, University of Florida, United States of America

  2. Nicholas M Kroeger
    Developer

    College of Engineering, University of Florida, United States of America

  3. Emily L Gill
    Developer

    Department of Chemistry, University of Florida, United States of America

  4. Candice Z Ulmer
    Developer

    Hollings Marine Laboratory, National Institute of Standards and Technology, United States of America

  5. John A Bowden
    Developer

    Hollings Marine Laboratory, National Institute of Standards and Technology, United States of America

  6. Rainey E Patterson
    Developer

    Department of Chemistry, University of Florida, United States of America

  7. Richard A Yost
    Developer

    Department of Pathology, Immunology, United States of America

  8. Timothy J Garrett
    Investigator

    Department of Pathology, Immunology, United States of America

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Summary
AccessionBT005980
Tool TypeApplication
Category
PlatformsWindows
TechnologiesR
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByTimothy J Garrett