ArticlePLoS computational biology2021
Pathway analysis in metabolomics: Recommendations for the use of over-representation analysis.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Sex-biased transcriptomic landscapes in bipolar disorder: integrating neurobiology and clinical heterogeneity through cross-study meta-analysis.Biology of sex differences · 2026Pooled it
- Demonstrating the reliability of in vivo metabolomics-based chemical grouping: Part 2 - Consistency of group-specific metabolic effects.Archives of toxicology · 2026Article
- Integrated metabolomics data analysis to generate mechanistic hypotheses with MetaProViz.Molecular systems biology · 2026Article
- Metabolic profiling of Escherichia coli under deuterium oxide-induced stress.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Network propagation in bipartite metabolite-reaction graphs for metabolomic data exploration.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- MetaboGraph: A Framework for Metabolomics and Lipidomics Annotation and Pathway Network Analysis.Analytical chemistry · 2026Article
- Metabolomic Insights on Obesity and Diabetes from Feeding Diets Varying in Carbohydrate-Fat Ratios in Zucker Diabetic Fatty (ZDF) and Lean Zucker (ZInternational journal of molecular sciences · 2026Article
- High-Quality Predicted Metabolite-Pathway Annotations Expand Pathway Coverage and Increase Enriched Pathway Detection Across Metabolomics Datasets.Metabolites · 2026Article
- Nutritional, Mineral, Taste, and Metabolic Profiles ofFoods (Basel, Switzerland) · 2026Article
- Targeted Serum Organic-Acid Profiling Identifies Candidate Metabolic Signatures in Peripartum Cardiomyopathy: A Case-Control Study.International journal of molecular sciences · 2026Article
- Trends in Computational Metabolomics: A Perspective on Five Years of Software Development, Challenges, and Opportunities (2021-2025).Analytical chemistry · 2026Review
- A Reporting Guideline for Observational Studies in Metabolomic Epidemiology: Explanation and Elaboration of the Strobe-MetEpi Checklist.Research square · 2026Article
- Metabolomic insights into inter-familial and pre-transport treatment effects on live transport stress in selectively-bred mussels, Perna canaliculus.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Integrative Multi-Omics Reveals Microbiome and Genome Streamlining Underlie Ecological Divergence in Chinese and XinjiangInternational journal of molecular sciences · 2026Article
- Differential metabolomic prediction of outcomes in HFpEF and HFrEF: a prospective international multi-ethnic cohort study.Cardiovascular research · 2026Article
- Roles of Metabolomics in Allergic Rhinitis: From Cell to Bedside Investigations.International journal of molecular sciences · 2026Review
- Endothelial dysfunction and metabolic biomarkers in post-COVID-19 syndrome.Scientific reports · 2026Article
- Influence of Gut Microbiota on Immune Responses and Protection in Volunteers Receiving the Live Attenuated Oral ETEC Vaccine ACE257 followed by Virulent ETEC H10407 Challenge.Research square · 2026Article
- Navigating multi-omic integration methods for human microbiome research.Nature microbiology · 2026Review
- An Overview of Metabolomic Approaches to Polyphenol Profiling for Nutraceutical Development.Molecules (Basel, Switzerland) · 2026Review
61 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
Over-representation analysis (ORA) is one of the commonest pathway analysis approaches used for the functional interpretation of metabolomics datasets. Despite the widespread use of ORA in metabolomics, the community lacks guidelines detailing its best-practice use. Many factors have a pronounced impact on the results, but to date their effects have received little systematic attention. Using five publicly available datasets, we demonstrated that changes in parameters such as the background set, differential metabolite selection methods, and pathway database used can result in profoundly different ORA results. The use of a non-assay-specific background set, for example, resulted in large numbers of false-positive pathways. Pathway database choice, evaluated using three of the most popular metabolic pathway databases (KEGG, Reactome, and BioCyc), led to vastly different results in both the number and function of significantly enriched pathways. Factors that are specific to metabolomics data, such as the reliability of compound identification and the chemical bias of different analytical platforms also impacted ORA results. Simulated metabolite misidentification rates as low as 4% resulted in both gain of false-positive pathways and loss of truly significant pathways across all datasets. Our results have several practical implications for ORA users, as well as those using alternative pathway analysis methods. We offer a set of recommendations for the use of ORA in metabolomics, alongside a set of minimal reporting guidelines, as a first step towards the standardisation of pathway analysis in metabolomics.
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