Power of isotopic fine structure for unambiguous determination of metabolite elemental compositions: In silico evaluation and metabolomic application

Tatsuhiko Nagao, Daichi Yukihira, Yoshinori Fujimura, Kazunori Saito, Katsutoshi Takahashi, Daisuke Miura, Hiroyuki Wariishi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In mass spectrometry (MS)-based metabolomics studies, reference-free identification of metabolites is still a challenging issue. Previously, we demonstrated that the elemental composition (EC) of metabolites could be unambiguously determined using isotopic fine structure, observed by ultrahigh resolution MS, which provided the relative isotopic abundance (RIA) of 13C, 15N, 18O, and 34S. Herein, we evaluated the efficacy of the RIA for determining ECs based on the MS peaks of 20,258 known metabolites. The metabolites were simulated with a ≤25% error in the isotopic peak area to investigate how the error size effect affected the rate of unambiguous determination of the ECs. The simulation indicated that, in combination with reported constraint rules, the RIA led to unambiguous determination of the ECs for more than 90% of the tested metabolites. It was noteworthy that, in positive ion mode, the process could distinguish alkali metal-adduct ions ([M+Na]+ and [M+K]+). However, a significant degradation of the EC determination performance was observed when the method was applied to real metabolomic data (mouse liver extracts analyzed by infusion ESI), because of the influence of noise and bias on the RIA. To achieve ideal performance, as indicated in the simulation, we developed an additional method to compensate for bias on the measured ion intensities. The method improved the performance of the calculation, permitting determination of ECs for 72% of the observed peaks. The proposed method is considered a useful starting point for high-throughput identification of metabolites in metabolomic research.

Original languageEnglish
Pages (from-to)70-76
Number of pages7
JournalAnalytica Chimica Acta
Volume813
DOIs
Publication statusPublished - Feb 27 2014

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Metabolomics
Metabolites
Computer Simulation
metabolite
Mass Spectrometry
Ions
Chemical analysis
Mass spectrometry
mass spectrometry
Alkali Metals
Liver Extracts
ion
Noise
alkali metal
size effect
simulation
evaluation
Positive ions
Research
Throughput

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Environmental Chemistry
  • Spectroscopy

Cite this

Power of isotopic fine structure for unambiguous determination of metabolite elemental compositions : In silico evaluation and metabolomic application. / Nagao, Tatsuhiko; Yukihira, Daichi; Fujimura, Yoshinori; Saito, Kazunori; Takahashi, Katsutoshi; Miura, Daisuke; Wariishi, Hiroyuki.

In: Analytica Chimica Acta, Vol. 813, 27.02.2014, p. 70-76.

Research output: Contribution to journalArticle

Nagao, Tatsuhiko ; Yukihira, Daichi ; Fujimura, Yoshinori ; Saito, Kazunori ; Takahashi, Katsutoshi ; Miura, Daisuke ; Wariishi, Hiroyuki. / Power of isotopic fine structure for unambiguous determination of metabolite elemental compositions : In silico evaluation and metabolomic application. In: Analytica Chimica Acta. 2014 ; Vol. 813. pp. 70-76.
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