Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition

Abstract This study explored the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD), focusing on autophagy-related genes and their immune infiltration during the transition from AKI to CKD. We performed weighted correlation network analysis (WGCNA) using two microarray d...

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Main Authors: Yaojun Wang, Qiang Li
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97269-9
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author Yaojun Wang
Qiang Li
author_facet Yaojun Wang
Qiang Li
author_sort Yaojun Wang
collection DOAJ
description Abstract This study explored the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD), focusing on autophagy-related genes and their immune infiltration during the transition from AKI to CKD. We performed weighted correlation network analysis (WGCNA) using two microarray datasets (GSE139061 and GSE66494) in the GEO database and identified autophagy signatures by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA enrichment analysis. Machine learning algorithms such as LASSO, random forest, and XGBoost were used to construct the diagnostic model, and the diagnostic performance of GSE30718 (AKI) and GSE37171 (CKD) was used as validation cohorts to evaluate its diagnostic performance. The study identified 14 autophagy candidate genes, among which ATP6V1C1 and COPA were identified as key biomarkers that were able to effectively distinguish between AKI and CKD. Immune cell infiltration and GSEA analysis revealed immune dysregulation in AKI, and these genes were associated with inflammation and immune pathways. Single-cell analysis showed that ATP6V1C1 and COPA were specifically expressed in AKI and CKD, which may be related to renal fibrosis. In addition, drug prediction and molecular docking analysis proposed SZ(+)-(S)-202-791 and PDE4 inhibitor 16 as potential therapeutic agents. In summary, this study provides new insights into the relationship between AKI and CKD and lays a foundation for the development of new treatment strategies.
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spelling doaj-art-de5cb0a64fd04e3386dbe428425e54092025-08-20T02:20:25ZengNature PortfolioScientific Reports2045-23222025-04-0115112010.1038/s41598-025-97269-9Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transitionYaojun Wang0Qiang Li1Clinical Medical College, Affiliated Hospital, Hebei UniversityDepartment of Dermatology, Air Force Medical Center, PLAAbstract This study explored the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD), focusing on autophagy-related genes and their immune infiltration during the transition from AKI to CKD. We performed weighted correlation network analysis (WGCNA) using two microarray datasets (GSE139061 and GSE66494) in the GEO database and identified autophagy signatures by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA enrichment analysis. Machine learning algorithms such as LASSO, random forest, and XGBoost were used to construct the diagnostic model, and the diagnostic performance of GSE30718 (AKI) and GSE37171 (CKD) was used as validation cohorts to evaluate its diagnostic performance. The study identified 14 autophagy candidate genes, among which ATP6V1C1 and COPA were identified as key biomarkers that were able to effectively distinguish between AKI and CKD. Immune cell infiltration and GSEA analysis revealed immune dysregulation in AKI, and these genes were associated with inflammation and immune pathways. Single-cell analysis showed that ATP6V1C1 and COPA were specifically expressed in AKI and CKD, which may be related to renal fibrosis. In addition, drug prediction and molecular docking analysis proposed SZ(+)-(S)-202-791 and PDE4 inhibitor 16 as potential therapeutic agents. In summary, this study provides new insights into the relationship between AKI and CKD and lays a foundation for the development of new treatment strategies.https://doi.org/10.1038/s41598-025-97269-9AKI; CKDAutophagyBiomarkersMachine learning
spellingShingle Yaojun Wang
Qiang Li
Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition
Scientific Reports
AKI; CKD
Autophagy
Biomarkers
Machine learning
title Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition
title_full Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition
title_fullStr Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition
title_full_unstemmed Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition
title_short Integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated AKI to CKD transition
title_sort integrated multiomics analysis identifies potential biomarkers and therapeutic targets for autophagy associated aki to ckd transition
topic AKI; CKD
Autophagy
Biomarkers
Machine learning
url https://doi.org/10.1038/s41598-025-97269-9
work_keys_str_mv AT yaojunwang integratedmultiomicsanalysisidentifiespotentialbiomarkersandtherapeutictargetsforautophagyassociatedakitockdtransition
AT qiangli integratedmultiomicsanalysisidentifiespotentialbiomarkersandtherapeutictargetsforautophagyassociatedakitockdtransition