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Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.

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.

SUBMITTER: Baron C

PROVIDER: S-EPMC10709128 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.

Baron Cantin C Cherkaoui Sarah S Therrien-Laperriere Sandra S Ilboudo Yann Y Poujol Raphaël R Mehanna Pamela P Garrett Melanie E ME Telen Marilyn J MJ Ashley-Koch Allison E AE Bartolucci Pablo P Rioux John D JD Lettre Guillaume G Rosiers Christine Des CD Ruiz Matthieu M Hussin Julie G JG

iScience 20231114 12

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 ...[more]

PMID: 38077122

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Dataset Information

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.

Publications

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.

Similar Datasets

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