Implications of cytokines in Memory B cell for risk stratification and therapeutic framework construction among Pediatric Influenza patents: insights from machine learning and multi-omics.

OBJECTIVE: Cytokine storm and dysregulation of Memory B cell aggravate the symptoms and weaken the therapeutic effectiveness for Pediatric Influenza(PI) patents. Hence, deeper understanding of Integration cytokines and memory B cell can pave the way for the treatment of PI. METHODS: By integration of 2 peripheral blood bulk profiles of PI patients(GSE29366 and GSE42026) and integrative bioinformatic analysis, including CIBERSORT, WGCNA, Limma and 3 machine learning algorithms(RF, Lasso and SVM-RFE), we creatively identified Memory B cell-associated differentially expressed cytokines and hub cytokine for PI patients. Next, dignostic potential of hub cytokine was estimated in aforementioned 2 bulk profiles and independent validation peripheral blood bulk profiles of PI patients(GSE50628). Besides, consensus clustering empowered the molecular subgroups identification for PI patients based on Memory B cell-associated differentially expressed cytokines. Indeed, molecular and immune features were also estimated in peripheral blood bulk profile of PI patients (GSE42026) and peripheral blood single-cell transcriptomic profile of PI patients(GSE243629). Finally, therapeutic repurposing agent targeting hub cytokine for treatment of PI was assessed by DGIDB database and validated by molecular docking. RESULTS: MYD88 can be considered as up-regulated expression and Memory B cell distributed hub cytokine involved in PI pathogenesis, which illustrated favorable dignostic performance. Besides, 5 differentially expressed cytokines can divide PI patients into 2 consensus subgroups. Finally, Zanubrutinib can be considered as optimal therapeutic reproposing strategy targeting MYD88 for the treatment of PI. CONCLUSION: Our study first revelated MYD88 can be considered as Memory B cell distribution cytokine serving for the diagnosis and treatment of PI patients.