bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Abstract Untargeted metabolomics provides a direct window into biochemical activities but faces critical challenges in determining metabolite origins and interpreting unannotated metabolic features. Here, we present TidyMass2, an enhanced computational framework for Liquid Chromatography-Mass Spectrometry (LC-MS) untargeted that addresses these limitations. TidyMass2 introduces three major innovations compared its predecessor, TidyMass: (1) comprehensive origin inference capability traces metabolites to human, microbial, dietary, pharmaceutical, environmental sources through integration of 11 databases containing 532,488 with source information; (2) feature-based functional module analysis approach bypasses the annotation bottleneck by leveraging network topology extract biological insights from features; (3) intuitive graphical interface makes advanced analyses accessible researchers without programming expertise. Applied longitudinal urine data human pregnancy, identified diverse originating microbiome, environment, uncovered 27 dysregulated modules. It increased proportion biologically interpretable features 5.8% 58.8%, revealing coordinated changes steroid hormone biosynthesis, carbohydrate metabolism, amino acid processing. By expanding interpretation beyond conventionally MS 2 spectra-based annotated metabolites, enables more phenotyping while upholding strict open-source principles reproducibility, traceability, transparency.

Language: Английский