Identification and analysis of differently expressed transcription factors in aristolochic acid nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38777778", "kind": "science-record", "revision": 5, "content_hash": "sha256:52c2d2cb7f7f153c6661eeaa8da822ae511070b6bc096b16cf39e35270287348", "created_at": "2026-11-01T19:20:44Z", "updated_at": "2026-11-01T22:54:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and analysis of differently expressed transcription factors in aristolochic acid nephropathy.", "doi": "10.1265/ehpm.23-00245", "pmid": "38777778", "authors": ["Yi-Feng Wu", "Zhi-Yao Tang", "Yi-Xuan Deng", "Kun Liu", "Xu-Rui Gu", "Guang-Liang Zhou", "Yu-Jie Huang", "Xiao-Qing Lin", "Lin-Yun Zhou", "Xiao-Cong Zuo"], "journal": "Environmental health and preventive medicine", "year": 2024, "abstract": "BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited.\nMETHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN.\nRESULTS: Our analysis identified 88 co-DEGs through the \"limma\" and \"WGCNA\" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model.\nCONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.", "claims": [{"id": "claim-method", "statement": "Then, we performed difference analysis using the limma package between the control and AAN groups in GSE27168 and GSE136276 datasets. Genes displaying an absolute log fold change (log FC) above 1 and a P-value below 0.05 were categorized as DEGs. Using the GSE136276 gene expression data, we constructed a scale-free network via the R package WGCNA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38777778", "locator": "sections[3] \"2.1 GEO datasets selection and DEGs screening\" paragraph 2", "quote": "Then, we performed difference analysis using the limma package between the control and AAN groups in GSE27168 and GSE136276 datasets. Genes displaying an absolute log fold change (log FC) above 1 and a P-value below 0.05 were categorized as DEGs. Using the GSE136276 gene expression data, we constructed a scale-free network via the R package WGCNA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38777778", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our analysis identified 88 co-DEGs through the “limma” and “WGCNA” R packages.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38777778", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our analysis identified 88 co-DEGs through the “limma” and “WGCNA” R packages."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our analysis identified 88 co-DEGs through the “limma” and “WGCNA” R packages.", "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:38777778"], "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:GSE136276"], "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:GSE136276"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38777778", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1265/ehpm.23-00245", "sha256": "sha256:5c4ded92fd653bc7f9fb3a2df55dcbf21cfdbcd5507839a0da6ac8e4ce2e7e28", "bytes": 33132, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1265/ehpm.23-00245", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11157247", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE136276", "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=GSE136276", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE136276", "version": null, "note": "The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4043919", "GSM4043920", "GSM4043921", "GSM4043922", "GSM4043923", "GSM4043924", "GSM4043925", "GSM4043926", "GSM4043927", "GSM4043928", "GSM4043929", "GSM4043930", "GSM4043931", "GSM4043932", "GSM4043933", "GSM4043934", "GSM4043935", "GSM4043936", "GSM4043937", "GSM4043938", "GSM4043939", "GSM4043940", "GSM4043941", "GSM4043942", "GSM4043943", "GSM4043944", "GSM4043945", "GSM4043946", "GSM4043947", "GSM4043948"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "23038", "taxon": "Mus musculus", "title": "The impact of p53 on aristolochic acid I-induced gene expression in vivo", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE27168", "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=GSE27168", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27168", "version": null, "note": "The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM671534", "GSM671535", "GSM671536", "GSM671537", "GSM671538", "GSM671539", "GSM671540", "GSM671541", "GSM671542", "GSM671543", "GSM671544", "GSM671545"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data in HK-2 cells following exposure to Aa_hd", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE136276 not downloaded", "asset:data:geo:GSE136276 licence not read", "asset:data:geo:GSE27168 not downloaded", "asset:data:geo:GSE27168 licence not read"]}, "analysis": {"state": "complete", "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": "Then, we performed difference analysis using the limma package between the control and AAN groups in GSE27168 and GSE136276 datasets. Genes displaying an absolute log fold change (log FC) above 1 and a P-value below 0.05 were categorized as DEGs. Using the GSE136276 gene expression data, we constructed a scale-free network via the R package WGCNA."}}, {"id": "method-2", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-3", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "targets": [], "gaps": []}, "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": ["GSE27168", "GSE136276"], "resolved_accessions": ["GSE27168", "GSE136276"], "statements": ["The datasets used in this study can be obtained by contacting the corresponding author upon reasonable request."], "basis": "The paper names GSE27168, GSE136276 in Gene Expression Omnibus (GEO) 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:38777778", "data:geo:GSE136276"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE136276"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:19:13Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10224, "completion_tokens": 1208, "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:38777778", "type": "paper", "label": "pmid:38777778"}, {"id": "source:pmid:38777778", "type": "manuscript", "label": "PMID 38777778 full text"}, {"id": "data:geo:GSE136276", "type": "dataset", "label": "GEO GSE136276"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38777778", "type": "paper", "label": "pmid:38777778"}, {"id": "source:pmid:38777778", "type": "manuscript", "label": "PMID 38777778 full text"}, {"id": "data:geo:GSE136276", "type": "dataset", "label": "GEO GSE136276"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38777778", "type": "extraction", "used": ["source:pmid:38777778"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE136276", "type": "accession_resolution", "used": ["data:geo:GSE136276"], "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:38777778", "parent_hash": "sha256:a1586afce96611f0773628c11dd60861263857a4a0ae97d696d8fe52cd32ac28", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE136276 licence not read", "asset:data:geo:GSE136276 not downloaded", "asset:data:geo:GSE27168 licence not read", "asset:data:geo:GSE27168 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["ions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention wa", "Central South University (Changsha, China). Mice were housed under controlled conditions (12:12 li", "water. Following a week of acclimatization, mice were randomly assigned to two groups: AAN (n = 6)"], "order_basis": "paper_text_order:1288", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["N, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress an", "were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to", "two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN,"], "order_basis": "paper_text_order:1319", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["on of 40 µmol/L AA. The Cell Counting Kit 8 (CCK8, Apexbio) assay was used to detect cell viab"], "order_basis": "paper_text_order:2808", "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": ["Then, we performed difference analysis using the limma package between the control and AAN groups in GSE27168 and GSE136276 datasets. Genes displaying an absolute log fold change (log FC) above 1 and a P-value below 0.05 were categorized as DEGs. Using the GSE136276 gene expression data, we constructed a scale-free network via the R package WGCNA."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}