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As wine quality is directly linked to fruit quality, studying grapevine metabolism is important to understand the processes underlying grape composition. Genome-scale metabolic models (GSMMs) have been used for the study of plant metabolism and advances have been made, allowing the integration of omics datasets with GSMMs. On the other hand, Machine learning (ML) has been used to analyze and integrate omics data, and while the combination of ML with GSMMs has shown promising results, it is still scarcely used to study plants. Here, the first GSSM of <jats:italic>V<\/jats:italic>. <jats:italic>vinifera<\/jats:italic> was reconstructed and validated, comprising 7199 genes, 5399 reactions, and 5141 metabolites across 8 compartments. Tissue-specific models for the stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases. The potential of combining ML with GSMMs was explored by using ML to analyze the fluxomics data generated by green and mature grape GSMMs and provide insights regarding the metabolism of grapes at different developmental stages. Therefore, the models developed in this work are useful tools to explore different aspects of grapevine metabolism and understand the factors influencing grape quality.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012506","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T17:37:46Z","timestamp":1728581866000},"page":"e1012506","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["A diel multi-tissue genome-scale metabolic model of Vitis 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