Background Jerusalem artichoke (Helianthus tuberosus L.) is a highly stress-resistant crop, especially it grows normally in the desertified land of Qinghai-Tibet Plateau in the past two years, and has become a crop with agricultural, industrial and ecological functions. However, there are few studies on drought resistance of Jerusalem artichoke at present, and studies on the mechanisms of stress resistance of Jerusalem artichoke breeding and fructan are seriously lagging behind. In this study,

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... e selected two differentially resistant cultivars for drought stress experiments with different concentration gradients, the aim was finding DEGs and metabolic pathways associated with drought stress. Results Based on an additional analysis of the metabolic pathways under drought stress using MapMan, the most different types of metabolism included secondary metabolism, light reaction metabolism and cell wall. As a whole, QY1 and QY3 both had a large number of up-regulated genes in the flavor pathway. It was suggested that flavonoids could help Jerusalem artichoke to resist drought stress and maintain normal metabolic activities. In addition, the gene analysis of the abscisic acid (ABA) key metabolic pathway showed that QY3 had more genes in NAC and WRKY than QY1, but QY1 had more genes in response to drought stress as a whole. By combining RNA-Seq and WGCNA, a weighted gene co-expression network was constructed and divided into modules. By analyzing specifically the expressed modules, four modules were found to have the highest correlation with drought. Further research on the genes revealed that all 16 genes related to histone, ABA and protein kinase had the highest significance in these pathways. Conclusions These findings represent the first RNA-Seq analysis of drought stress in Jerusalem artichoke, which is of substantial significance to explore the function of drought resistance in Jerusalem artichoke and the excavation of related genes.