Bioinformatic analyses of hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36198577", "kind": "science-record", "revision": 5, "content_hash": "sha256:d4c136c8872f32d628dd5c174af88833b57b8d1b7c44fe17c8813108ef4f81a5", "created_at": "2026-11-01T18:15:30Z", "updated_at": "2026-11-01T22:50:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatic analyses of hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function.", "doi": "10.1265/ehpm.22-00023", "pmid": "36198577", "authors": ["Zemin Cai", "Wei Hu", "Ruotong Wu", "Shukai Zheng", "Kusheng Wu"], "journal": "Environmental health and preventive medicine", "year": 2022, "abstract": "BACKGROUND: Polybrominated diphenyl ethers (PBDEs) and their metabolites have severe impact on human health, but few studies focus on their nephrotoxicity. This study was conceived to explore hub genes that may be involved in two hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function.\nMETHODS: Gene dataset was obtained from Gene Expression Omnibus (GEO). Principal component analysis and correlation analysis were used to classify the samples. Differentially expressed genes (DEGs) were screened using the limma package in RStudio (version 4.1.0). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome enrichment analyses of DEGs were conducted. Protein-protein interaction (PPI) network was established using STRING network, and genes were filtered by Cytoscape (version 3.8.2). Finally, the hub genes were integrated by plug-in CytoHubba and RobustRankAggreg, and were preliminarily verified by the Comparative Toxicogenomics Database (CTD).\nRESULTS: GSE8588 dataset was selected in this study. About 190 upregulated and 224 downregulated DEGs in 2-OH-BDE47 group, and 244 upregulated and 276 downregulated DEGs in 2-OH-BDE85 group. Functional enrichment analyses in the GO, KEGG and Reactome indicated the potential involvement of DEGs in endocrine metabolism, oxidative stress mechanisms, regulation of abnormal cell proliferation, apoptosis, DNA damage and repair. 2-OH-BDE85 is more cytotoxic in a dose-dependent manner than 2-OH-BDE47. A total of 98 hub genes were filtered, and 91 nodes and 359 edges composed the PPI network. Besides, 9 direct-acting genes were filtered for the intersection of hub genes by CTD.\nCONCLUSIONS: OH-PBDEs may induce H295R adrenocortical cancer cells in the disorder of endocrine metabolism, regulation of abnormal cell proliferation, DNA damage and repair. The screened hub genes may play an important role in this dysfunction.", "claims": [{"id": "claim-method", "statement": "The limma [33] was used to explore the significant differentially expressed RNAs in samples from cells with 2-OH-BDE47 or 2-OH-BDE85 and normal samples. The false discovery rate (FDR) was used to calculate the statistical significance of multiple inspection. Genes with FDR <0.05 and Log2[Fold Change] (Log2[FC]) > 1 were considered as DEGs and were visualized through volcano plot.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36198577", "locator": "sections[4] \"2.2 Identification of differentially expressed genes\" paragraph 2", "quote": "The limma [33] was used to explore the significant differentially expressed RNAs in samples from cells with 2-OH-BDE47 or 2-OH-BDE85 and normal samples. The false discovery rate (FDR) was used to calculate the statistical significance of multiple inspection. Genes with FDR <0.05 and Log2[Fold Change] (Log2[FC]) > 1 were considered as DEGs and were visualized through volcano plot."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets of PBDEs and their derivatives affect adrenal steroidogenesis in H295R adrenocortical cancer cells were acquired from GEO database, please visit: https://www.ncbi.nlm.nih.gov/geo.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36198577", "locator": "sections[19] \"Availability of data and material\" paragraph 2", "quote": "The datasets of PBDEs and their derivatives affect adrenal steroidogenesis in H295R adrenocortical cancer cells were acquired from GEO database, please visit: https://www.ncbi.nlm.nih.gov/geo."}], "state": "complete"}, {"id": "claim-target-result", "statement": "About 603 significant DEGs (278 upregulated and 325 downregulated DEGs) were found in 2-OH-BDE47 group, and 705 significant DEGs (339 upregulated and 366 downregulated DEGs) were found in 2-OH-BDE85 group (Fig. 2).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36198577", "locator": "sections[8] \"3.1 Identification of differentially expressed genes\" paragraph 2", "quote": "About 603 significant DEGs (278 upregulated and 325 downregulated DEGs) were found in 2-OH-BDE47 group, and 705 significant DEGs (339 upregulated and 366 downregulated DEGs) were found in 2-OH-BDE85 group (Fig. 2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "About 603 significant DEGs (278 upregulated and 325 downregulated DEGs) were found in 2-OH-BDE47 group, and 705 significant DEGs (339 upregulated and 366 downregulated DEGs) were found in 2-OH-BDE85 group (Fig. 2).", "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:36198577"], "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:GSE8588"], "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": {"fdr_threshold": "limma with false discovery rate (FDR) correction"}, "inputs": ["data:geo:GSE8588"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36198577", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1265/ehpm.22-00023", "sha256": "sha256:f1184fa156d66e73d940ec866ec98031879e287269b6a222b6f15cb8cce3d146", "bytes": 37609, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1265/ehpm.22-00023", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9556975", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE8588", "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=GSE8588", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE8588", "version": null, "note": "The datasets of PBDEs and their derivatives affect adrenal steroidogenesis in H295R adrenocortical cancer cells were acquired from GEO database, please visit: https://www.ncbi.nlm.nih.gov/geo.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets of PBDEs and their derivatives affect adrenal steroidogenesis in H295R adrenocortical cancer cells were acquired from GEO database, please visit: https://www.ncbi.nlm.nih.gov/geo.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM213193", "GSM213194", "GSM213197", "GSM213199", "GSM213200", "GSM213201", "GSM213204", "GSM213205", "GSM213210"], "sample_count": 9, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "OH-PBDE-induced gene expression profiling in H295R adrenocortical carcinoma cells", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE8588 not downloaded", "asset:data:geo:GSE8588 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": {"fdr_threshold": "limma with false discovery rate (FDR) correction"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The limma [33] was used to explore the significant differentially expressed RNAs in samples from cells with 2-OH-BDE47 or 2-OH-BDE85 and normal samples. The false discovery rate (FDR) was used to calculate the statistical significance of multiple inspection. Genes with FDR <0.05 and Log2[Fold Change] (Log2[FC]) > 1 were considered as DEGs and were visualized through volcano plot."}}, {"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": 0.7, "band": "medium", "quote": "Principal component analysis"}}, {"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": ["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": ["GSE8588"], "resolved_accessions": ["GSE8588"], "statements": ["The datasets of PBDEs and their derivatives affect adrenal steroidogenesis in H295R adrenocortical cancer cells were acquired from GEO database, please visit: https://www.ncbi.nlm.nih.gov/geo."], "basis": "The paper names GSE8588 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:36198577", "data:geo:GSE8588"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE8588"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:08:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11596, "completion_tokens": 1579, "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:36198577", "type": "paper", "label": "pmid:36198577"}, {"id": "source:pmid:36198577", "type": "manuscript", "label": "PMID 36198577 full text"}, {"id": "data:geo:GSE8588", "type": "dataset", "label": "GEO GSE8588"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36198577", "type": "paper", "label": "pmid:36198577"}, {"id": "source:pmid:36198577", "type": "manuscript", "label": "PMID 36198577 full text"}, {"id": "data:geo:GSE8588", "type": "dataset", "label": "GEO GSE8588"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36198577", "type": "extraction", "used": ["source:pmid:36198577"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE8588", "type": "accession_resolution", "used": ["data:geo:GSE8588"], "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:36198577", "parent_hash": "sha256:83d92513984c5337fb22b24f628f31f60bf18128388d8c77141176fa0a3d3ad0", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE8588 licence not read", "asset:data:geo:GSE8588 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": [", regulation of abnormal cell proliferation, apoptosis, DNA damage and repair. 2-OH-BDE85 is more c"], "order_basis": "paper_text_order:1503", "id": "assay:1"}, {"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 limma [33] was used to explore the significant differentially expressed RNAs in samples from cells with 2-OH-BDE47 or 2-OH-BDE85 and normal samples. The false discovery rate (FDR) was used to calculate the statistical significance of multiple inspection. Genes with FDR <0.05 and Log2[Fold Change] (Log2[FC]) > 1 were considered as DEGs and were visualized through volcano plot."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}