Identification and Analysis of Hub Genes in Diabetic Cardiomyopathy: Potential Role of Cytochrome P450 1A1 in Mitochondrial Metabolism and STZ-Induced Myocardial Dysfunction.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35387435", "kind": "science-record", "revision": 5, "content_hash": "sha256:5d28c6eb0ce8fdbb119061539dc2417cf0b1528aa1b6fabeedc8a1e4a3c052f3", "created_at": "2026-11-01T18:14:12Z", "updated_at": "2026-11-01T22:48:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Analysis of Hub Genes in Diabetic Cardiomyopathy: Potential Role of Cytochrome P450 1A1 in Mitochondrial Metabolism and STZ-Induced Myocardial Dysfunction.", "doi": "10.3389/fcvm.2022.835244", "pmid": "35387435", "authors": ["Yinliang Chen", "Jinbao Yang", "Ying Wang", "Weike Shen", "Jinlin Liu", "Meng Yuan", "Xiaoyu Hao", "Li Zhong", "Rui Guo"], "journal": "Frontiers in cardiovascular medicine", "year": 2022, "abstract": "Diabetic cardiomyopathy (DCM) is a primary cause of death in diabetic patients; however, its molecular mechanism is not yet clear, and there is no uniform standard for diagnosis. The aim of this study is to discover the pathogenesis and potential therapeutic targets of DCM through screening and analysis of differentially expressed genes (DEGs) in heart ventricles of DCM, and to testify the role of key hub genes in DCM-induced myocardial dysfunction. Datasets GSE4745 and GSE6880 were downloaded from the GEO database. The difference analysis, visual analysis, cluster analysis and enrichment analysis were performed by using R language, python scripts and bioinformatics software followed by the construction of protein-protein interaction (PPI) network to obtain hub genes. The DCM models were established by streptozocin (STZ) injection to the male mice. The cardiac function and the expressions of hub genes were examined by using echocardiography and real-time quantitative poly-merase chain reaction (RT-qPCR), followed by multiple statistical analyses. Bioinformatic results indicate that mitochondrial dysfunction, disturbed lipid metabolism and decreased collagen synthesis are the main causes of the DCM development. In particular, the hub gene Cyp1a1 that encodes Cytochrome P450 1A1 (CYP4501A1) enzyme has the highest connectivity in the interaction network, and is associated with mitochondrial homeostasis and energy metabolism. It plays a critical role in the oxidation of endogenous or exogenous substrates. Our RT-qPCR results confirmed that ventricular Cyp1a1 mRNA level was nearly 12-fold upregulated in DCM model compared to normal control, which was correlated with abnormal cardiac function in diabetic individuals. CYP4501A1 protein expression in mitochondria was also increased in diabetic hearts. However, we found no significant changes in collagen expressions in cardiac ventricles of mice with DCM. This study provided compact data support for understanding the pathogenesis of DCM. CYP4501A1 might be considered as a potential candidate targeting for DCM therapy. Follow-up animal and clinical verifications need to be further explored.", "claims": [{"id": "claim-method", "statement": "Subsequently, the normalized microarray data were analyzed by using the limma package of R for DEGs identification.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35387435", "locator": "sections[4] \"Data Acquisition and Identification of DEGs\" paragraph 2", "quote": "Subsequently, the normalized microarray data were analyzed by using the limma package of R for DEGs identification."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35387435", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 212 DEGs in GSE4745 and 396 DEGs in GSE6880, including 37 common DEGs in diabetic ventricles compared with normal controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35387435", "locator": "sections[14] \"Screening and Identification of DEGs Between Healthy and Diabetic Ventricles\" paragraph 2", "quote": "A total of 212 DEGs (105 up-regulated and 107 down-regulated) in GSE4745, and 396 DEGs in GSE6880 (205 up-regulated and 191 down-regulated) were screened, among which, 37 common DEGs including 20 upregulated genes and 17 downregulated genes were identified in diabetic ventricles compared to normal controls (Figure 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The analysis identified 212 DEGs in GSE4745 and 396 DEGs in GSE6880, including 37 common DEGs in diabetic ventricles compared with normal controls.", "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:35387435"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": {"log2fc_threshold": "with genes selected at logFC ≥1 or logFC ≤−1 and adj"}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35387435", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2022.835244", "sha256": "sha256:0d752a6a526acfdc8c843bf23f3f289eb078aacb7967e464154f546b0fef1b7a", "bytes": 56495, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2022.835244", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8977650", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "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": {"log2fc_threshold": "with genes selected at logFC ≥1 or logFC ≤−1 and adj"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Subsequently, the normalized microarray data were analyzed by using the limma package of R for DEGs identification."}}, {"id": "method-2", "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"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "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": "R4", "reachable": false, "accessions": ["GSE4745 and GSE6880"], "resolved_accessions": [], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE4745 and GSE6880, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:35387435"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:40:53Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15842, "completion_tokens": 1362, "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:35387435", "type": "paper", "label": "pmid:35387435"}, {"id": "source:pmid:35387435", "type": "manuscript", "label": "PMID 35387435 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35387435", "type": "paper", "label": "pmid:35387435"}, {"id": "source:pmid:35387435", "type": "manuscript", "label": "PMID 35387435 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35387435", "type": "extraction", "used": ["source:pmid:35387435"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:35387435", "parent_hash": "sha256:a1588cf6fdf955c68bbb79d8f520524cce2a505d9973dd2a4ff907508c2ec80f", "fork_of": null, "generation": 4}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"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": ["ime quantitative poly-merase chain reaction (RT-qPCR), followed by multiple statistical analyses.", "n of endogenous or exogenous substrates. Our RT-qPCR results confirmed that ventricular Cyp1a1 mR", "quantitative poly-merase chain reaction (RT-qPCR), followed by multiple statistical analyses.", "f endogenous or exogenous substrates. Our RT-qPCR results confirmed that ventricular Cyp1a1 mR"], "order_basis": "paper_text_order:1140", "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": ["the mice. Briefly, 9-week-old male C57BL/6N mice were subjected to intraperitoneal injections of S", "echocardiographic analysis (28). The female mice were not used because estrogen may have an import"], "order_basis": "paper_text_order:2630", "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": ["Subsequently, the normalized microarray data were analyzed by using the limma package of R for DEGs identification."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}