Analysis and Validation of Autophagy-Related Gene Biomarkers and Immune Cell Infiltration Characteristic in Bronchopulmonary Dysplasia by Integrating Bioinformatics and Machine Learning.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39839185", "kind": "science-record", "revision": 4, "content_hash": "sha256:fe830db444144a87ea328e7e641b02ee6b6739242873951dcafaba41a1ba4baf", "created_at": "2026-11-01T20:30:08Z", "updated_at": "2026-11-01T22:56:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis and Validation of Autophagy-Related Gene Biomarkers and Immune Cell Infiltration Characteristic in Bronchopulmonary Dysplasia by Integrating Bioinformatics and Machine Learning.", "doi": "10.2147/JIR.S495132", "pmid": "39839185", "authors": ["Shuzhe Xiao", "Yue Ding", "Chen Du", "Yiting Lv", "Shumei Yang", "Qi Zheng", "Zhiqiu Wang", "Qiaoli Zheng", "Meifang Huang", "Qingyan Xiao", "Zhuxiao Ren", "Guangliang Bi", "Jie Yang"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Background: Autophagy and immunity play important regulatory roles in lung developmental disorders. However, there is currently a lack of bioinformatics analysis on autophagy-related genes (ARGs) and immune infiltration in bronchopulmonary dysplasia (BPD). We aim to screen and validate the signature genes of BPD by bioinformatics and in vivo experiment.\nMethods: GSE8586 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the R program. Using cell-type identification with CIBERSORT to analyze the inflammatory and immune status of BPD. Subsequently, the hub genes were identified by Lasso and Cytoscape with three machine-learning algorithms (MCC, Degree and MCODE). In addition, hub genes were validated with ROC, single-cell sequence and IHC in hyperoxia rats. Finally, we searched the drug targets of these hub genes, and established a nomogram model for predicting the risk of BPD.\nResults: There were 73 the differentially expressed and autophagy-related genes (DE-ARGs) by overlapping the DEGs in GSE8586 and ARGs. Five hub genes, BRIX1, JUN, PES1, NR4A1 and RRP9, were lowly expressed in the BPD group and had high diagnostic value in the diagnostic model. All hub genes are mainly located in B cell, epithelial cell, fibroblast, endothelial cell, smooth muscle cell and pneumocyte in lung single-cell sequencing. Moreover, immune infiltration analysis showed immune cells were higher in the BPD group and were closely associated with hub genes. We also predict the drug targets of the genes. Finally, the IHC result in rats showed that expression of PES1, BRX1, RRP9, JUN, NR4A1 was lower in the hyperoxia group compared to the normoxia group.\nConclusion: BRIX1, JUN, PES1, NR4A1, RRP9, may be promising therapeutic targets for BPD. Our findings provided researchers and clinicians with more evidence regarding immunotherapeutic strategies for BPD treatment.", "claims": [{"id": "claim-method", "statement": "The DEGs between normal and BPD groups in the GSE8586 dataset were identified using the limma package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39839185", "locator": "sections[4] \"Sample Detection and Differential Expression Genes Analysis\" paragraph 2", "quote": "The DEGs between normal and BPD groups in the GSE8586 dataset were identified using the limma package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39839185", "locator": "sections[34] \"Data Sharing Statement\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Five hub genes, BRIX1, JUN, PES1, NR4A1 and RRP9, were lowly expressed in the BPD group and had high diagnostic value in the diagnostic model.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39839185", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Five hub genes, BRIX1, JUN, PES1, NR4A1 and RRP9, were lowly expressed in the BPD group and had high diagnostic value in the diagnostic model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Five hub genes, BRIX1, JUN, PES1, NR4A1 and RRP9, were lowly expressed in the BPD group and had high diagnostic value in the diagnostic model.", "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:39839185"], "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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Methods: GSE8586 was obtained fr", "argets of the genes. Finally, the IHC result in rats showed that expression of PES1, BRX1, RRP9,", "C, single-cell sequence and IHC in hyperoxia rats. Finally, we searched the drug targets of th", "ets of the genes. Finally, the IHC result in rats showed that expression of PES1, BRX1, RRP9,"], "order_basis": "paper_text_order:478", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["validated with ROC, single-cell sequence and IHC in hyperoxia rats. Finally, we searched the", "the drug targets of the genes. Finally, the IHC result in rats showed that expression of PES", "natal day 14 (P14). (C and D) Representative immunohistochemical plots of ARGs in rats' lung tissue. The anal", "O2 rats than in 21% O2 rats (Figure 8B). The IHC results showed that expression of PES1, BRX1"], "order_basis": "paper_text_order:960", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The DEGs between normal and BPD groups in the GSE8586 dataset were identified using the limma package."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}