Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35845072", "kind": "science-record", "revision": 5, "content_hash": "sha256:0aec727b3db5cc0acb2354ae2bc4be6f30056dd6201d8d03a47b265249d0600b", "created_at": "2026-11-01T18:14:55Z", "updated_at": "2026-11-01T22:49:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis.", "doi": "10.3389/fcvm.2022.890321", "pmid": "35845072", "authors": ["Yue Zheng", "Bingcai Qi", "Wenqing Gao", "Zhenchang Qi", "Yanwu Liu", "Yuchao Wang", "Jianyu Feng", "Xian Cheng", "Zhiqiang Luo", "Tong Li"], "journal": "Frontiers in cardiovascular medicine", "year": 2022, "abstract": "Background: The macrophages are involved in all stages of cardiovascular diseases, demonstrating the correlation between inflammation, atherosclerosis, and myocardial infarction (MI). Here, we aim to investigate macrophages-related genes in the deterioration of atherosclerosis.\nMethods: GSE41571 was downloaded and the abundance of immune cells was estimated by utilizing the xCell. By utilizing the limma test and correlation analysis, differentially expressed macrophages-related genes (DEMRGs) were documented. The functional pathways and the protein-protein interaction (PPI) network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the expressions of hub DEMRGs were analyzed using the GSE135055 and GSE116250 datasets as well as atherosclerosis and MI mice model.\nResults: A total of 509 differentially expressed genes (DEGs) were correlated with the abundance of macrophages and were identified as DEMRGs (Pearson correlation coefficients (PCC) > 0.6), which were mainly enriched in extracellular structure organization, lysosomal membrane, MHC protein complex binding, and so on. After screening out, 28 hub DEMRGs were obtained with degrees ≥20, including GNAI1 (degree = 113), MRPS2 (degree = 56), HCK (degree = 45), SOCS3 (degree = 40), NET1 (degree = 28), and so on. After validating using Gene Expression Omnibus (GEO) datasets and the atherosclerosis and MI mice model, eight proteins were validated using ApoE-/- and C57 mice. The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.\nConclusion: The screened hub DEMRGs, SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, EIF4EBP1, and PPP4C, may be therapeutic targets for treatment and prediction in the patients with plaque progression and MI recurrent events. The kit of the eight hub DEMRGs may test plaque progression and MI recurrent events and help in the diagnosis and treatment of MI-induced heart failure (HF), thus decreasing mortality and morbidity.", "claims": [{"id": "claim-method", "statement": "The differentially expressed genes (DEGs) were explored by utilizing the “limma” package. Log2|fold change|>1 and p < 0.05 were the thresholds. Then, Pearson correlation analysis was applied to obtain the DEGs related to macrophages. The DEGs with Pearson correlation coefficients (PCC) >0.6 were regarded as DEMRGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35845072", "locator": "sections[5] \"Identification of DEMRGs\" paragraph 2", "quote": "The differentially expressed genes (DEGs) were explored by utilizing the “limma” package. Log2|fold change|>1 and p < 0.05 were the thresholds. Then, Pearson correlation analysis was applied to obtain the DEGs related to macrophages. The DEGs with Pearson correlation coefficients (PCC) >0.6 were regarded as DEMRGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35845072", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35845072", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.", "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:35845072"], "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:GSE116250"], "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:GSE116250"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35845072", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2022.890321", "sha256": "sha256:fc8f64b769a3ca3cb61245d498b37e90d06c8a90aaf41ca503a94632a0a254cc", "bytes": 33965, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2022.890321", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9282674", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE116250", "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=GSE116250", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE116250", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3219558", "GSM3219559", "GSM3219560", "GSM3219561", "GSM3219562", "GSM3219563", "GSM3219564", "GSM3219565", "GSM3219566", "GSM3219567", "GSM3219568", "GSM3219569", "GSM3219570", "GSM3219571", "GSM3219572", "GSM3219573", "GSM3219574", "GSM3219575", "GSM3219576", "GSM3219577", "GSM3219578", "GSM3219579", "GSM3219580", "GSM3219581", "GSM3219582", "GSM3219583", "GSM3219584", "GSM3219585", "GSM3219586", "GSM3219587", "GSM3219588", "GSM3219589", "GSM3219590", "GSM3219591", "GSM3219592", "GSM3219593", "GSM3219594", "GSM3219595", "GSM3219596", "GSM3219597", "GSM3219598", "GSM3219599", "GSM3219600", "GSM3219601", "GSM3219602", "GSM3219603", "GSM3219604", "GSM3219605", "GSM3219606", "GSM3219607", "GSM3219608", "GSM3219609", "GSM3219610", "GSM3219611", "GSM3219612", "GSM3219613", "GSM3219614", "GSM3219615", "GSM3219616", "GSM3219617", "GSM3219618", "GSM3219619", "GSM3219620", "GSM3219621"], "sample_count": 64, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "RNA-seq of heart failure in human left ventricles", "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:GSE135055", "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=GSE135055", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE135055", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3984434", "GSM3984435", "GSM3984436", "GSM3984437", "GSM3984438", "GSM3984439", "GSM3984440", "GSM3984441", "GSM3984442", "GSM3984443", "GSM3984444", "GSM3984445", "GSM3984446", "GSM3984447", "GSM3984448", "GSM3984449", "GSM3984450", "GSM3984451", "GSM3984452", "GSM3984453", "GSM3984454", "GSM3984455", "GSM3984456", "GSM3984457", "GSM3984458", "GSM3984459", "GSM3984460", "GSM3984461", "GSM3984462", "GSM3984463", "GSM3984464", "GSM3984465", "GSM3984466", "GSM3984467", "GSM3984468", "GSM3984469", "GSM3984470", "GSM3984471", "GSM3984472", "GSM3984473", "GSM3984474", "GSM3984475", "GSM3984476", "GSM3984477", "GSM3984478", "GSM3984479", "GSM3984480", "GSM3984481", "GSM3984482", "GSM3984483", "GSM3984484", "GSM3984485", "GSM3984486", "GSM3984487", "GSM3984488", "GSM3984489", "GSM3984490", "GSM3984491", "GSM3984492", "GSM3984493"], "sample_count": 60, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE163154", "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=GSE163154", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE163154", "version": null, "note": "Publicly available datasets were analyzed in this study. 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Log2|fold change|>1 and p < 0.05 were the thresholds. Then, Pearson correlation analysis was applied to obtain the DEGs related to macrophages. The DEGs with Pearson correlation coefficients (PCC) >0.6 were regarded as DEMRGs."}}, {"id": "method-2", "family": "group_comparison", "specific": "welch_t_test", "label": "Group comparison", "dsl_operations": ["welch_t"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Welch's t-test"}}, {"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": 0.7, "band": "medium", "quote": "Pearson correlation"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-5", "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": ["GSE41571", "GSE163154", "GSE135055", "GSE116250"], "resolved_accessions": ["GSE41571", "GSE163154", "GSE135055", "GSE116250"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: The data, including GSE41571, GSE163154, GSE135055, and GSE116250 were downloaded from the Gene Expression Omnibus (GEO) dataset."], "basis": "The paper names GSE41571, GSE163154, GSE135055, GSE116250 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:35845072", "data:geo:GSE116250"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE116250"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:55:32Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10221, "completion_tokens": 1753, "cached_tokens": 256}}, "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:35845072", "type": "paper", "label": "pmid:35845072"}, {"id": "source:pmid:35845072", "type": "manuscript", "label": "PMID 35845072 full text"}, {"id": "data:geo:GSE116250", "type": "dataset", "label": "GEO GSE116250"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35845072", "type": "paper", "label": "pmid:35845072"}, {"id": "source:pmid:35845072", "type": "manuscript", "label": "PMID 35845072 full text"}, {"id": "data:geo:GSE116250", "type": "dataset", "label": "GEO GSE116250"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35845072", "type": "extraction", "used": ["source:pmid:35845072"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE116250", "type": "accession_resolution", "used": ["data:geo:GSE116250"], "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:35845072", "parent_hash": "sha256:22e6b7e9a6558374b358e4c90e8a50e4ea44abc405c11c6668d3a61a3bc75b2b", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE116250 licence not read", "asset:data:geo:GSE116250 not downloaded", "asset:data:geo:GSE135055 licence not read", "asset:data:geo:GSE135055 not downloaded", "asset:data:geo:GSE163154 licence not read", "asset:data:geo:GSE163154 not downloaded", "asset:data:geo:GSE41571 licence not read", "asset:data:geo:GSE41571 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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": 1.0, "evidence": ["The differentially expressed genes (DEGs) were explored by utilizing the “limma” package. Log2|fold change|>1 and p < 0.05 were the thresholds. Then, Pearson correlation analysis was applied to obtain the DEGs related to macrophages. The DEGs with Pearson correlation coefficients (PCC) >0.6 were regarded as DEMRGs."], "order_basis": "analysis_only", "id": "assay:1"}]}