Integrated transcriptomic and metabolomic analyses identify key metabolites and genes in sepsis-associated acute lung injury
- 1Medical Inspection Center, The Second Hospital Affiliated to Liaoning University of Traditional Chinese Medicine
- 2Pharmacological Laboratory, Liaoning Provincial Academy of Traditional Chinese Medicine
- 3Animal Experimental Center, Liaoning Provincial Academy of Traditional Chinese Medicine
Abstract
Introduction: Sepsis-associated acute lung injury (SALI) is a life-threatening pulmonary complication of sepsis with high mortality. This study aimed to prioritize serum metabolites and genes potentially involved in SALI by integrating multi-omics datasets.
Methods: A rat SALI model treated with Xuanbai Chengqi Decoction (XCD) was subjected to untargeted serum metabolomics. Bulk and single-cell RNA-seq datasets were retrieved from GEO, and metabolite-related GWAS statistics were obtained from IEU OpenGWAS. scPagwas mapped metabolite genetic signals to cell populations; hdWGCNA identified cell signature genes. Candidate genes were filtered by overlapping bulk DEGs, ten machine-learning models and expression validation. Functional enrichment, immune infiltration, cell -cell communication, pseudotime and scTenifoldKnk virtual knockdown analyses were performed.
Results: Oleoylcarnitine showed the strongest genetic association with T cells. Cross-platform integration prioritized GIMAP4 and RCBTB2 as hub genes, with WBP2 retained for further validation. Their expression correlated with altered immune infiltration, especially eosinophils, and the three-gene profiles shared 62 biological processes. SALI exhibited increased number and strength of cell interactions compared with isolated sepsis. Five T-cell subsets were identified, and virtual knockdown of hub genes modified regulation of eight DEGs.
Discussion: Oleoylcarnitine-associated metabolic changes are correlated with T-cell dysregulation mediated by GIMAP4, RCBTB2, and WBP2 in SALI. These findings are descriptive, and further experiments are required to establish causal relationships.
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BibTeX
@article{huang2026integrated,
title = {{Integrated transcriptomic and metabolomic analyses identify key metabolites and genes in sepsis-associated acute lung injury}},
author = {He Huang and Lei Zhao and He Chen and Ling Sui and Jinghe Zhu and Xiaonan Fang and Pengzhuo Li and He Liu and Xiaolin Wu and Decheng Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1959223},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959223/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated transcriptomic and metabolomic analyses identify key metabolites and genes in sepsis-associated acute lung injury
AU - He Huang
AU - Lei Zhao
AU - He Chen
AU - Ling Sui
AU - Jinghe Zhu
AU - Xiaonan Fang
AU - Pengzhuo Li
AU - He Liu
AU - Xiaolin Wu
AU - Decheng Wang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1959223
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959223/full
AB - Introduction: Sepsis-associated acute lung injury (SALI) is a life-threatening pulmonary complication of sepsis with high mortality. This study aimed to prioritize serum metabolites and genes potentially involved in SALI by integrating multi-omics datasets. Methods: A rat SALI model treated with Xuanbai Chengqi Decoction (XCD) was subjected to untargeted serum metabolomics. Bulk and single-cell RNA-seq datasets were retrieved from GEO, and metabolite-related GWAS statistics were obtained from IEU OpenGWAS. scPagwas mapped metabolite genetic signals to cell populations; hdWGCNA identified cell signature genes. Candidate genes were filtered by overlapping bulk DEGs, ten machine-learning models and expression validation. Functional enrichment, immune infiltration, cell -cell communication, pseudotime and scTenifoldKnk virtual knockdown analyses were performed. Results: Oleoylcarnitine showed the strongest genetic association with T cells. Cross-platform integration prioritized GIMAP4 and RCBTB2 as hub genes, with WBP2 retained for further validation. Their expression correlated with altered immune infiltration, especially eosinophils, and the three-gene profiles shared 62 biological processes. SALI exhibited increased number and strength of cell interactions compared with isolated sepsis. Five T-cell subsets were identified, and virtual knockdown of hub genes modified regulation of eight DEGs. Discussion: Oleoylcarnitine-associated metabolic changes are correlated with T-cell dysregulation mediated by GIMAP4, RCBTB2, and WBP2 in SALI. These findings are descriptive, and further experiments are required to establish causal relationships.
SN - 1664-3224
ER -