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Background   Neonatal sepsis (NS) is considered as the most common cause of neonatal deaths that newborns suffer from. Although numerous studies focus on gene biomarkers of NS, the predictive value of the gene biomarkers is low. NS pathogenesis is still needed to be investigated.Methods   After data preprocessing, we used KEGG enrichment method to identify the differentially expressed pathways between NS and normal controls. Then, functional principal component analysis (FPCA) was adopted to calculate gene values in NS. In order to further study the key signaling pathway of the NS, elastic-net regression model, Mann–Whitney  U  test, and coexpression network were used to estimate the weights of signaling pathway and hub genes.Results   A total of 115 different pathways between NS and controls were first identified. FPCA made full use of time-series gene expression information and estimated  F  values of genes in the different pathways. The top 1000 genes were considered as the different genes and were further analyzed by elastic-net regression and MWU test. There were 7 key signaling pathways between the NS and controls, according to different sources. Among those genes involved in key pathways, 7 hub genes, PIK3CA, TGFBR2, CDKN1B, KRAS, E2F3, TRAF6, and CHUK, were determined based on the coexpression network. Most of them were cancer-related genes. PIK3CA was considered as the common marker, which is highly expressed in the lymphocyte group. Little was known about the correlation of PIK3CA with NS, which gives us a new enlightenment for NS study.Conclusion   This research might provide the perspective information to explore the potential novel genes and pathways as NS therapy targets.

Potential Genes and Pathways of Neonatal Sepsis Based on Functional Gene Set Enrichment Analyses