Identification and Verification of Feature Biomarkers Associated With Immune Cells in Dilated Cardiomyopathy by Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35646094", "kind": "science-record", "revision": 4, "content_hash": "sha256:ad0ed9d388f13afe5e8c9271861a060b4224829d2d9343f284cf06217a3b5136", "created_at": "2026-11-01T18:14:34Z", "updated_at": "2026-11-01T22:06:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Verification of Feature Biomarkers Associated With Immune Cells in Dilated Cardiomyopathy by Bioinformatics Analysis.", "doi": "10.3389/fgene.2022.874544", "pmid": "35646094", "authors": ["Tingfang Zhu", "Mingjie Wang", "Jinwei Quan", "Zunhui Du", "Qiheng Li", "Yuan Xie", "Menglu Lin", "Cathy Xu", "Yucai Xie"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Objective: To explore immune-related feature genes in patients with dilated cardiomyopathy (DCM). Methods: Expression profiles from three datasets (GSE1145, GSE21610 and GSE21819) of human cardiac tissues of DCM and healthy controls were downloaded from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were identified by the 'limma' package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed to identify biological functions of the DEGs. The compositional patterns of stromal and immune cells were estimated using xCell. Hub genes and functional modules were identified based on protein-protein interaction (PPI) network analysis by STRING webtool and Cytoscape application. Correlation analysis was performed between immune cell subtypes and hub genes. Hub genes with |correlation coefficient| > 0.5 and p value <0.05 were selected as feature biomarkers. A logistic regression model was constructed based on the selected biomarkers and validated in datasets GSE5406 and GSE57338. Results: A total of 1,005 DEGs were identified. Functional enrichment analyses indicated that extracellular matrix remodeling and immune and inflammation disorder played important roles in the pathogenesis of DCM. Immune cells, including CD8+ T-cells, macrophages M1 and Th1 cells, were proved to be significantly changed in DCM patients by immune cell infiltration analysis. In the PPI network analysis, STAT3, IL6, CCL2, PIK3R1, ESR1, CCL5, IL17A, TLR2, BUB1B and MYC were identified as hub genes, among which CCL2, CCL5 and TLR2 were further screened as feature biomarkers by using hub genes and immune cells correlation analysis. A diagnosis model was successfully constructed by using the three biomarkers with area under the curve (AUC) scores 0.981, 0.867 and 0.946 in merged dataset, GSE5406 and GSE57338, respectively. Conclusion: The present study identified three immune-related genes as diagnostic biomarkers for DCM, providing a novel perspective of immune and inflammatory response for the exploration of DCM molecular mechanisms.", "claims": [{"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: GSE1145; GSE21610; GSE29819; GSE5406; GSE57338.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35646094", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: GSE1145; GSE21610; GSE29819; GSE5406; GSE57338."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified CCL2, CCL5, and TLR2 as diagnostic biomarkers and developed a three-gene diagnostic model for DCM with AUC values of 0.981, 0.867, and 0.946 in the merged dataset, GSE5406, and GSE57338, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35646094", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A diagnosis model was successfully constructed by using the three biomarkers with area under the curve (AUC) scores 0.981, 0.867 and 0.946 in merged dataset, GSE5406 and GSE57338, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified CCL2, CCL5, and TLR2 as diagnostic biomarkers and developed a three-gene diagnostic model for DCM with AUC values of 0.981, 0.867, and 0.946 in the merged dataset, GSE5406, and GSE57338, respectively.", "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:35646094"], "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:GSE1145"], "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:GSE1145"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35646094", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.874544", "sha256": "sha256:9354a7d8666988d11cf582664fb69dc012bc40689c538ca20f3cb8be4c0622d4", "bytes": 28101, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2022.874544", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9133742", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1145", "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=GSE1145", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1145", "version": null, "note": "Publicly available datasets were analyzed in this study. 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"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": ["GSE1145", "GSE21610", "GSE29819", "GSE5406", "GSE57338"], "resolved_accessions": ["GSE1145", "GSE21610", "GSE29819", "GSE5406", "GSE57338"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: GSE1145; GSE21610; GSE29819; GSE5406; GSE57338."], "basis": "The paper names GSE1145, GSE21610, GSE29819, GSE5406, GSE57338 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:35646094", "data:geo:GSE1145"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE1145"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:48:17Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8094, "completion_tokens": 2751, "cached_tokens": 188}}, "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:35646094", "type": "paper", "label": "pmid:35646094"}, {"id": "source:pmid:35646094", "type": "manuscript", "label": "PMID 35646094 full text"}, {"id": "data:geo:GSE1145", "type": "dataset", "label": "GEO GSE1145"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35646094", "type": "paper", "label": "pmid:35646094"}, {"id": "source:pmid:35646094", "type": "manuscript", "label": "PMID 35646094 full text"}, {"id": "data:geo:GSE1145", "type": "dataset", "label": "GEO GSE1145"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35646094", "type": "extraction", "used": ["source:pmid:35646094"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE1145", "type": "accession_resolution", "used": ["data:geo:GSE1145"], "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:35646094", "parent_hash": "sha256:ea2ec047cc93e02e101830adb9c51f392e52ef993dbd09b03f5f5686e6c708cb", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE1145 licence not read", "asset:data:geo:GSE1145 not downloaded", "asset:data:geo:GSE21610 licence not read", "asset:data:geo:GSE21610 not downloaded", "asset:data:geo:GSE29819 licence not read", "asset:data:geo:GSE29819 not downloaded", "asset:data:geo:GSE5406 licence not read", "asset:data:geo:GSE5406 not downloaded", "asset:data:geo:GSE57338 licence not read", "asset:data:geo:GSE57338 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": 0.7, "evidence": ["limma"], "order_basis": "analysis_only", "id": "assay:1"}]}