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In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
Key genes identified in ammonia-induced cell death during pediatric sepsis: Machine learning, single-cell, and
Yong Feng Huang1, Xing Chuan Li2, Ran Jiang1
1Lanzhou University, Lanzhou, Gansu, 730030, PR China.
Background:
Sepsis is a life-threatening organ dysfunction caused by a dysregulated immune response to infection. Ammonia-induced cell death (AICD) is a novel form of cell death, and its association with sepsis remains unclear. This study aims to identify key genes involved in AICD in pediatric sepsis.
Method:
Obtain batch transcriptome (bulk RNA) and single-cell transcriptome (scRNA) data of pediatric sepsis from the Gene Expression Omnibus (GEO) database. Screen for differentially expressed genes (DEGs) and key module genes of weighted gene co-expression networks in the bulk RNA data, and take the intersection with AICD-related genes. Construct diagnostic models using various machine learning algorithms and identify key genes. Evaluate immune infiltration using CIBERSORT. Analyze the expression characteristics of key genes using scRNA-seq and conduct cell communication analysis. Further perform functional enrichment analysis under virtual gene knockout conditions using scTenifoldKnk.
Result:
The optimal diagnostic model identified a total of 9 key genes for pediatric sepsis AICD (STOM, SORT1, PADI4, MMP9, LCN2, CR1, TSPO, TXN, IL1RN). The immune infiltration analysis revealed that the proportions of cells such as Macrophages M0 and Neutrophils increased in the sepsis group, while the proportions of T cells CD8 and B cells naive decreased. Single-cell analysis showed that TSPO and TXN were upregulated in Monocytes in the sepsis group. After virtual knockout of TSPO and TXN, the perturbed genes are respectively enriched in pathways such as the B cell receptor signaling pathway and Platelet activation, and jointly enriched in pathways including Hematopoietic cell lineage.
Conclusion:
This study identified nine genes, including TSPO and TXN, as key genes for AICD in pediatric sepsis. The diagnostic model constructed has potential clinical application value. Monocytes may be the potential cell type that undergoes AICD in the high-ammonia environment of pediatric sepsis. TSPO and TXN may affect the AICD process of pediatric sepsis through different mechanisms.
