ArticleiScience2023
Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Vitiligo Information Resource database v3.NPJ systems biology and applications · 2026Article
- Computational approaches to enzymatic reaction assignment: a review of methods, validations, and future directions.Briefings in bioinformatics · 2025Review
- Application of GWAS and mGWAS in Livestock and Poultry Breeding.Animals : an open access journal from MDPI · 2024Review
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Abstract
Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks.
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Registered trials
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