Flaxseed (Linum usitatissimum L.) is a valuable functional food known for its rich content of omega-3 fatty acids, lignans, α-linolenic acid, and high-quality proteins. The primary goal of this research was to explore the potential sleep-enhancing effects of flaxseed through network-based analysis. Differentially expressed genes (DEGs) associated with flaxseed intake were obtained from the GSE36422 dataset in the Gene Expression Omnibus (GEO) repository. Genes linked to sleep were retrieved from the GeneCards database and subjected to undirected protein-protein interaction (PPI) network evaluation to identify central hub genes. Overlapping DEGs and hub genes were identified as key targets influenced by flaxseed. These hub genes were further examined using directed PPI networks to determine the roles of overlapping genes and their immediate interactors. Among 212 hubs related to sleep, RAF1 emerged as a prominent hub gene. Evaluation of sleep-associated hubs revealed that MAPK family members, CCND1, KRAS, RAF1, PIK3CA, and EGFR acted as major regulators, while HRAS, AKT1, IL6, RHOA, TNF, SRC, FOXO3, CDC42, PRKACG, PRKACB, MAPK8, and JAK2 were key downstream targets. The MAPK family, KRAS, and PIK3CA were highlighted as essential direct interactors of RAF1. Results suggest that RAF1, a central sleep-related hub gene, is downregulated following flaxseed intake. This downregulation of RAF1, along with modulation of MAPK family members, KRAS, and PIK3CA, may contribute to enhanced sleep quality.
