Isotopic Ratio Outlier Analysis (IROA) for Quantitative Analysis

Abstract

Metabolomics is an omics science that tries to measure the metabolic composition of a sample rapidly, but the current state of the art cannot provide the reproducibility or accuracy needed for clinical use or even daily reproducibility for larger experiments. The IROA TruQuant Workflow uses a daily long-term reference standard (LTRS) and a chemically identical Internal Standard (IS) to provide validated chemical identity, accurate reproducible quantitation, and daily QA/QC (Quality Assurance / Quality Control) on instrument and sample preparation. It does this for hundreds of compounds, generating comparable measurements across days, instruments, and chromatographic methods. All the compounds in the LTRS are isotopically signed with formula-indicating IROA patterns, ensuring they cannot be mistaken as artifacts. These patterns allow software-driven analysis to determine daily instrument performance in terms of sensitivity, in-source fragmentation, chromatographic and injection stability, and to provide reproducible quantitation.

Keywords: Clinical metabolomics; Dual-MSTUS Normalization; Error-corrected quantitation; IROA TruQuant Workflow; Isotopic ratio outlier analysis; MS error correction; Metabolic profiling; Metabolomics Internal Standard; Metabolomics normalization; Suppression correction.