Background Foxtail millet ( Setaria italica L.) is an important minor cereal crop cultivated in arid and semi-arid regions. However, the molecular mechanisms determining variations in its edible quality remain unclear. In this study, 12 foxtail millet varieties were subjected to systematic edible quality evaluation. The molecular basis of quality differences between high- and low-quality varieties was elucidated by integrating comparative transcriptomics and untargeted metabolomics analyses. Results Flavor, grain color, and palatability were the key indicators of variety quality. Transcriptomic analysis identified 667 differentially expressed genes. Up-regulated genes were significantly enriched in phenylpropanoid biosynthesis, flavonoid/anthocyanin biosynthesis, and terpenoid metabolism pathways, whereas down-regulated genes were enriched in defense response and plant-pathogen interaction pathways. Nineteen key genes were identified, including those encoding flavanone 3-dioxygenase ( F3H ), dihydroflavonol 4-reductase ( DFR ), and anthocyanin 3- O -glucosyltransferase ( 3GT ). Metabolomic analysis detected 455 differential metabolites, 50 of which were significantly differential. Combined pathway analysis revealed a molecular network wherein high-quality varieties activated flavonoid/anthocyanin synthesis and terpenoid metabolism pathways with significant accumulation of homoplantaginin, delphinidin, kaempferide, myristicin, and (-)- trans -carveol. Meanwhile, these varieties suppressed defense responses and pectin synthesis, which reduced the content of bitter metabolites such as ingenol and cichorioside B and optimized the cell wall structure, may collectively contribute to improved edible quality. Conclusions This study systematically elucidated the molecular basis of edible quality differences in foxtail millet from a multi-omics perspective, providing candidate genes for genetic improvement.
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Ma et al. (2026) studied this question.
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