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.