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pmid:37576152
Identification of Hub Genes in the Pathogenesis of Bronchiolitis Obliterans via Bioinformatic Analysis and Experimental Verification.
Zhongji Wu · Xiaowen Chen · Kangkang Zhang · Zhenwei Liu · Haidi Zhang · Zhaocong Zheng · Xiaodie Zhang · Yubiao Chen · Yinghui Peng · Hui Li · Kaiyin Huang · Sixiang Tang · Li Zhao · Dehui Chen
Journal of inflammation research · 2023 doi:10.2147/JIR.S419845
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Experiment
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Complete file
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However, the precise molecular mechanism underlying BO remains unclear. We aimed to identify BO-associated hub genes and their molecular mechanisms.\nMethods: BO-associated transcriptome datasets (GSE52761, GSE137169, and GSE94557) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Additional bioinformatics analyses, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, were performed to determine functional roles and DEG-associated regulatory networks. Prediction of hub genes using the 12 algorithms available in the Cytohubba plugin of Cytoscape software was also performed. Verification was performed using the BO mouse model.\nResults: Our results revealed 57 DEGs associated with BO, of which 18 were down-regulated and 39 were up-regulated. The Cytohubba plugin data further narrowed down the 57 DEGs into 9 prominent hub genes (CCR2, CD1D, GM2A, TFEC, MPEG1, CTSS, GPNMB, BIRC2, and CTSZ). Genes such as CCR2, TFEC, MPEG1, CTSS, and CTSZ were dysregulated in 2,3-butanedione-induced BO mice, whereas TFEC, CTSS, and CTSZ were dysregulated in nitric acid-induced BO mouse models.\nConclusion: Our study identified and validated four novel BO biomarkers, which may allow further investigation into the development of distinct BO diagnostic markers and novel therapeutic avenues.", "claims": [{"id": "claim-method", "statement": "First, we transformed the matrix data into log2 values for data reduction; then, we utilized the R software package Limma (version 3.40.6) for data normalization and differential analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37576152", "locator": "sections[7] \"Data Processing and Differentially Expressed Genes Identification\" paragraph 2", "quote": "First, we transformed the matrix data into log2 values for data reduction; then, we utilized the R software package Limma (version 3.40.6) for data normalization and differential analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets were named GSE52761, GSE137169, and GSE94557 and involved the use of BO models in Wistar rats, in situ lung transplantation in C57 mice, and whole blood transcriptome sequencing in humans after lung transplantation, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37576152", "locator": "sections[16] \"Source of the Datasets\" paragraph 2", "quote": "The datasets were named GSE52761, GSE137169, and GSE94557 and involved the use of BO models in Wistar rats, in situ lung transplantation in C57 mice, and whole blood transcriptome sequencing in humans after lung transplantation, respectively."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 57 BO-associated DEGs, comprising 18 downregulated and 39 upregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37576152", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our results revealed 57 DEGs associated with BO, of which 18 were down-regulated and 39 were up-regulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 57 BO-associated DEGs, comprising 18 downregulated and 39 upregulated genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37576152"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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