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A Survey of Orbitrap All Ion Fragmentation Analysis Assessed by an R MetaboList Package to Study Small-Molecule Metabolites

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Abstract

Leukemia cell and melanoma tumor tissue extracts were studied for small (mostly m/z < 250) polar metabolites by LC-ESI-HRMSn analysis powered by a hybrid Quadrupole-Orbitrap. MS data were simultaneously acquired in fast polarity switching mode operating in MS1 and MS/MS (All Ion Fragmentation, AIF) full-scan analyses at high mass resolution. Positive metabolite assignments were achieved by AIF analysis considering at least two characteristic transitions. Targeted metabolite profiling was achieved by the relative quantification of 18 metabolites through spiking of their respective deuterated counterparts. Manual data processing of MS1 and AIF scans were compared for the accurate determination of natural metabolites and their deuterated analogs by chromatographic alignment and peak area integration. Evaluation of manual and automated (MetaboList R package) AIF data processing yielded comparable results. The versatility of AIF analysis also enabled the untargeted metabolite profiling of leukemia and melanoma samples in which 22 and 53 compounds were, respectively, identified outside those studied by labeling. The main limitation of this method was that low abundance metabolites with scan rates below 8 scans/peak could not be accurately quantified by AIF analysis. The combination of AIF analysis with MetaboList R package represents an opportunity to move towards automated, faster, and more global metabolomics approaches supported by an entirely flexible open source data processing platform freely available from Comprehensive R Archive Network (CRAN, https://CRAN.R-project.org/package=MetaboList).

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Funding

This work was supported by grants from the University of Texas System (ST: STAR Award), Hyundai Hope on Wheels research program, NIH R01 CA206210-01, and Cancer Prevention & Research Institute of Texas (CPRIT, DP150061).

Author information

Author notes

  1. Enrique Sentandreu, Manuel D. Peris-Díaz and Shannon R. Sweeney contributed equally to this work.

Authors and Affiliations

  1. Dell Pediatric Research Institute (DPRI), 1400 Barbara Jordan Blvd., Austin, TX, 78723, USA

    Enrique Sentandreu, Shannon R. Sweeney, Jennifer Chiou, Nathalie Muñoz & Stefano Tiziani

  2. Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA

    Enrique Sentandreu, Jennifer Chiou, Nathalie Muñoz & Stefano Tiziani

  3. Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA

    Shannon R. Sweeney & Stefano Tiziani

  4. Department of Chemical Biology, Faculty of Biotechnology, University of Wrocław, F. Joliot-Curie 14a, 50-383, Wrocław, Poland

    Manuel D. Peris-Díaz

Authors
  1. Enrique Sentandreu
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  2. Manuel D. Peris-Díaz
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  3. Shannon R. Sweeney
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  4. Jennifer Chiou
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  5. Nathalie Muñoz
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Corresponding author

Correspondence to Stefano Tiziani.

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Conflict of interest

Authors declare no conflict of interest.

Ethical approval for animal studies

All applicable international, national, and institutional guidelines for care and use of animals were followed. Study procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at The University of Texas at Austin prior to any murine experiments.

Ethical approval for human subjects

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Study procedures were approved by the Institutional Review Board (IRB) of both Seton Healthcare Family and The University of Texas at Austin prior to specimen collection.

Informed consent for human subjects

Informed consent was obtained from all individual participants included in this study. In the case of minors, informed consent was obtained from the participant’s legal guardians.

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Sentandreu, E., Peris-Díaz, M.D., Sweeney, S.R. et al. A Survey of Orbitrap All Ion Fragmentation Analysis Assessed by an R MetaboList Package to Study Small-Molecule Metabolites. Chromatographia 81, 981–994 (2018). https://doi.org/10.1007/s10337-018-3536-y

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  • DOI: https://doi.org/10.1007/s10337-018-3536-y

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