Bioinformatics-based analysis and experimental validation of PANoptosis-related biomarkers and immune infiltration in diabetic nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40958910", "kind": "science-record", "revision": 4, "content_hash": "sha256:c71505f3557b3a41fbab112ec13021a463e7c70178988c0814e92791f5319b2d", "created_at": "2026-11-01T20:31:02Z", "updated_at": "2026-11-01T22:57:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics-based analysis and experimental validation of PANoptosis-related biomarkers and immune infiltration in diabetic nephropathy.", "doi": "10.3389/fendo.2025.1610882", "pmid": "40958910", "authors": ["Su Zhang", "Yun Zhang", "Weitao Hu", "Chunyan Huang", "Yifang Zhang", "Xiaoqing Chen"], "journal": "Frontiers in endocrinology", "year": 2025, "abstract": "Background: Diabetic nephropathy (DN) is a frequent and serious microvascular complication of diabetes. PANoptosis is a novel mode of cell death that encompasses apoptosis, necrosis and pyroptosis. However, effective PANoptosis-related biomarkers for DN are currently lacking. Therefore, this study aimed to elucidate the role of PANoptosis-related genes (PRGs) in the development of DN and their potential as diagnostic markers of DN, as well as their association with immune cell infiltration.\nMaterials and methods: We retrieved the DN-related dataset GSE30122 from the GEO database. Then differentially expressed genes (DEGs) were identified and DEGs were analyzed for functional enrichment. In addition, we obtained key gene modules by WGCNA. Subsequently, we gained the intersecting genes of DEGs, key gene modules and PRGs. Four algorithms were further used to screen the key DE-PRGs in DN (DNDE-PRGs). We also investigated the biological functions of the key DNDE-PRGs by GSEA software. Furthermore, we analyzed the immune infiltration of DN tissues. The correlation of key genes with glomerular filtration rate (GFR) and blood urea nitrogen (BUN) was also examined. Finally, key genes were validated using clinical samples and db/db mice.\nResults: We identified two key DNDE-PRGs (AKT3 and FYN). They showed good diagnostic value in the DN. And they were associated with immune cell infiltration. In addition, they have a correlation with GFR and BUN. Finally, they were validated in clinical samples and animal experiments.\nConclusion: AKT3 and FYN may be good PANoptosis-related biomarkers in DN. This provides new insights into the pathogenesis of DN.", "claims": [{"id": "claim-method", "statement": "We carried out residue completion, background correction and normalization of GSE30122 with the “limma” package (17).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40958910", "locator": "sections[4] \"Preprocessing of GSE30122 and identification of differentially expressed genes\" paragraph 2", "quote": "We carried out residue completion, background correction and normalization of GSE30122 with the “limma” package (17)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40958910", "locator": "sections[38] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "AKT3 and FYN may be good PANoptosis-related biomarkers in DN.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40958910", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified two key DNDE-PRGs (AKT3 and FYN). They showed good diagnostic value in the DN. And they were associated with immune cell infiltration. In addition, they have a correlation with GFR and BUN. Finally, they were validated in clinical samples and animal experiments."}, {"asset": "source:pmid:40958910", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "AKT3 and FYN may be good PANoptosis-related biomarkers in DN. This provides new insights into the pathogenesis of DN."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "AKT3 and FYN may be good PANoptosis-related biomarkers in DN.", "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:40958910"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE30122"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE30122"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40958910", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2025.1610882", "sha256": "sha256:8a19f8ed30fd4b21b185c28ce4db6803ca287cf9dcb5948789614f65aa9b2222", "bytes": 40069, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2025.1610882", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12434962", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE30122", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30122", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30122", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM756992", "GSM756993", "GSM756994", "GSM756995", "GSM756996", "GSM756997", "GSM756998", "GSM756999", "GSM757000", "GSM757001", "GSM757002", "GSM757003", "GSM757004", "GSM757005", "GSM757006", "GSM757007", "GSM757008", "GSM757009", "GSM757010", "GSM757011", "GSM757012", "GSM757013", "GSM757014", "GSM757015", "GSM757016", "GSM757017", "GSM757018", "GSM757019", "GSM757020", "GSM757021", "GSM757022", "GSM757023", "GSM757024", "GSM757025", "GSM757026", "GSM757027", "GSM757028", "GSM757029", "GSM757030", "GSM757031", "GSM757032", "GSM757033", "GSM757034", "GSM757035", "GSM758485", "GSM758486", "GSM758487", "GSM758488", "GSM758489", "GSM758490", "GSM758491", "GSM758492", "GSM758493", "GSM758494", "GSM758495", "GSM758496", "GSM758497", "GSM758498", "GSM758499", "GSM758500", "GSM758501", "GSM758502", "GSM758503", "GSM758504", "GSM758505", "GSM758506", "GSM758507", "GSM758508", "GSM758509"], "sample_count": 69, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Transcriptome Analysis of Human Diabetic Kidney Disease", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE30528", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30528", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30528", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM756992", "GSM756993", "GSM756994", "GSM756995", "GSM756996", "GSM756997", "GSM756998", "GSM756999", "GSM757000", "GSM757001", "GSM757002", "GSM757003", "GSM757004", "GSM757005", "GSM757006", "GSM757007", "GSM757008", "GSM757009", "GSM757010", "GSM757011", "GSM757012", "GSM757013"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Glomeruli vs. Control Glomeruli)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE96804", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96804", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE96804", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2544275", "GSM2544276", "GSM2544277", "GSM2544278", "GSM2544279", "GSM2544280", "GSM2544281", "GSM2544282", "GSM2544283", "GSM2544284", "GSM2544285", "GSM2544286", "GSM2544287", "GSM2544288", "GSM2544289", "GSM2544290", "GSM2544291", "GSM2544292", "GSM2544293", "GSM2544294", "GSM2544295", "GSM2544296", "GSM2544297", "GSM2544298", "GSM2544299", "GSM2544300", "GSM2544301", "GSM2544302", "GSM2544303", "GSM2544304", "GSM2544305", "GSM2544306", "GSM2544307", "GSM2544308", "GSM2544309", "GSM2544310", "GSM2544311", "GSM2544312", "GSM2544313", "GSM2544314", "GSM2544315", "GSM2544316", "GSM2544317", "GSM2544318", "GSM2544319", "GSM2544320", "GSM2544321", "GSM2544322", "GSM2544323", "GSM2544324", "GSM2544325", "GSM2544326", "GSM2544327", "GSM2544328", "GSM2544329", "GSM2544330", "GSM2544331", "GSM2544332", "GSM2544333", "GSM2544334", "GSM2544335"], "sample_count": 61, "group_sizes": null, "group_sizes_basis": null, "platform": "17586", "taxon": "Homo sapiens", "title": "Exon Level Expression Profiling of Diabetic Nephropathy", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE30122 not downloaded", "asset:data:geo:GSE30122 licence not read", "asset:data:geo:GSE30528 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE96804 not downloaded", "asset:data:geo:GSE96804 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We carried out residue completion, background correction and normalization of GSE30122 with the “limma” package (17)."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE30122", "GSE30528", "GSE96804"], "resolved_accessions": ["GSE30122", "GSE30528", "GSE96804"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE30122, GSE30528, GSE96804 in GEO (Gene Expression Omnibus) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40958910", "data:geo:GSE30122"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30122"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:01:44Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11309, "completion_tokens": 1849, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40958910", "type": "paper", "label": "pmid:40958910"}, {"id": "source:pmid:40958910", "type": "manuscript", "label": "PMID 40958910 full text"}, {"id": "data:geo:GSE30122", "type": "dataset", "label": "GEO GSE30122"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40958910", "type": "paper", "label": "pmid:40958910"}, {"id": "source:pmid:40958910", "type": "manuscript", "label": "PMID 40958910 full text"}, {"id": "data:geo:GSE30122", "type": "dataset", "label": "GEO GSE30122"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40958910", "type": "extraction", "used": ["source:pmid:40958910"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30122", "type": "accession_resolution", "used": ["data:geo:GSE30122"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40958910", "parent_hash": "sha256:77b3db2802dd20f04cd19039103eb333b03545d207d0dfa5def86dd1bba1b695", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE30122 licence not read", "asset:data:geo:GSE30122 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE30528 not downloaded", "asset:data:geo:GSE96804 licence not read", "asset:data:geo:GSE96804 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["a novel mode of cell death that encompasses apoptosis, necrosis and pyroptosis. However, effective"], "order_basis": "paper_text_order:258", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ne was stored at -80°C for further analysis. Mice were sacrificed at 12th week. Kidney and blood samples were", "tion & grouping Six-week-aged db/m and db/db mice were purchased from Shanghai SLAC Co. The db/db m", "into db/m group (n=6) and db/db group (n=6). Mice were housed in individual metabolic cages for 24h", "ne was stored at -80°C for further analysis. Mice were sacrificed at 12th week. Kidney and blood sa"], "order_basis": "paper_text_order:2899", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["r than in the db/db group ( Figures 7E, F ). RT-qPCR results were consistent with IF staining ( F", "han in the db/db group ( Figures 7E, F ). RT-qPCR results were consistent with IF staining ( F"], "order_basis": "paper_text_order:6570", "id": "assay:3"}, {"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": ["We carried out residue completion, background correction and normalization of GSE30122 with the “limma” package (17)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}