Monitoring changes in the healthy female metabolome across the menstrual cycle using GC × GC-TOFMS

Jarrett Eshima, Stephanie Ong, Trenton J. Davis, Christopher Miranda, Devika Krishnamurthy, Abigael Nachtsheim, John Stufken, Christopher Plaisier, John Fricks, Heather Bean, Barbara Smith

Research output: Contribution to journalArticle

Abstract

Urinary metabolomics offers a non-invasive means of obtaining information about the system-wide biological health of a patient. Untargeted metabolomics approaches using one-dimensional gas chromatography (GC) are limited due to the chemical complexity of urine, which poorly detects co-eluting low-abundance analytes. Metabolite detection and identification can be improved by applying comprehensive two-dimensional GC, allowing for the discovery of additional viable biomarkers of disease. In this work, we applied comprehensive two-dimensional GC coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) to the analysis of urine samples collected daily across 28-days from 10 healthy female subjects for a personalized approach to female reproductive health monitoring. Through this analysis, we identified 935 unique volatile metabolites. Two statistical methods, a modified T-statistic and Wilcoxon Rank Sum, were applied to analyze differences in metabolome abundance on ovulation days as compared to non-ovulation days. Four metabolites (2-pentanone, 3-penten-2-one, carbon disulfide, acetone) were identified as statistically significant by the modified T-statistic but not the Rank Sum, after a false-discovery rate of 0.1 was set using a Benjamini-Hochberg correction. Subsequent analyses by boxplot indicated that the putative volatile metabolic biomarkers for fertility are expressed in increased or decreased abundance in urine on the day of ovulation. Individual analysis of metabolome expression across 28-days revealed some subject-specific features, which suggest a potential for long-term, personalized fertility monitoring using metabolomics.

Original languageEnglish (US)
Pages (from-to)48-57
Number of pages10
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1121
DOIs
StatePublished - Jul 15 2019

Fingerprint

Metabolome
Menstrual Cycle
Gas chromatography
Gas Chromatography
Metabolomics
Metabolites
Monitoring
Urine
Ovulation
Fertility
Biomarkers
Carbon Disulfide
Health
Statistics
Reproductive Health
Acetone
Information Systems
Gas Chromatography-Mass Spectrometry
Healthy Volunteers
Mass spectrometry

Keywords

  • Fertility
  • GC × GC-TOFMS
  • Ovulation
  • Personalized diagnostics
  • Urine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Monitoring changes in the healthy female metabolome across the menstrual cycle using GC × GC-TOFMS. / Eshima, Jarrett; Ong, Stephanie; Davis, Trenton J.; Miranda, Christopher; Krishnamurthy, Devika; Nachtsheim, Abigael; Stufken, John; Plaisier, Christopher; Fricks, John; Bean, Heather; Smith, Barbara.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1121, 15.07.2019, p. 48-57.

Research output: Contribution to journalArticle

Eshima, Jarrett ; Ong, Stephanie ; Davis, Trenton J. ; Miranda, Christopher ; Krishnamurthy, Devika ; Nachtsheim, Abigael ; Stufken, John ; Plaisier, Christopher ; Fricks, John ; Bean, Heather ; Smith, Barbara. / Monitoring changes in the healthy female metabolome across the menstrual cycle using GC × GC-TOFMS. In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2019 ; Vol. 1121. pp. 48-57.
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