An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38179058", "kind": "science-record", "revision": 3, "content_hash": "sha256:bc7b266841e4b49f0395e096b37967a2680e150bea2faeeef97e4c610394ba25", "created_at": "2026-11-01T19:20:06Z", "updated_at": "2026-11-01T22:10:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis.", "doi": "10.3389/fimmu.2023.1289223", "pmid": "38179058", "authors": ["Hong-Kai Cui", "Chao-Jie Tang", "Yu Gao", "Zi-Ang Li", "Jian Zhang", "Yong-Dong Li"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: The role of complement component 1q (C1Q) related genes on human atherosclerotic plaques (HAP) is less known. Our aim is to establish C1Q associated hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnose and predict HAP patients more effectively and investigate the association between C1Q and HAP (ischemic stroke) using bidirectional Mendelian randomization (MR) analysis.\nMethods: HAP scRNA-seq and bulk-RNA data were download from the Gene Expression Omnibus (GEO) database. The C1Q-related hub genes was screened using the GBM, LASSO and XGBoost algorithms. We built machine learning models to diagnose and distinguish between types of atherosclerosis using generalized linear models and receiver operating characteristics (ROC) analyses. Further, we scored the HALLMARK_COMPLEMENT signaling pathway using ssGSEA and confirmed hub gene expression through qRT-PCR in RAW264.7 macrophages and apoE-/- mice. Furthermore, the risk association between C1Q and HAP was assessed through bidirectional MR analysis, with C1Q as exposure and ischemic stroke (IS, large artery atherosclerosis) as outcomes. Inverse variance weighting (IVW) was used as the main method.\nResults: We utilized scRNA-seq dataset (GSE159677) to identify 24 cell clusters and 12 cell types, and revealed seven C1Q associated DEGs in both the scRNA-seq and GEO datasets. We then used GBM, LASSO and XGBoost to select C1QA and C1QC from the seven DEGs. Our findings indicated that both training and validation cohorts had satisfactory diagnostic accuracy for identifying patients with HPAs. Additionally, we confirmed SPI1 as a potential TF responsible for regulating the two hub genes in HAP. Our analysis further revealed that the HALLMARK_COMPLEMENT signaling pathway was correlated and activated with C1QA and C1QC. We confirmed high expression levels of C1QA, C1QC and SPI1 in ox-LDL-treated RAW264.7 macrophages and apoE-/- mice using qPCR. The results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013-1.234, P = 0.027).\nConclusion: The authors have effectively developed and validated a novel diagnostic signature comprising two genes for HAP, while MR analysis has provided evidence supporting a favorable association of C1Q on IS.", "claims": [{"id": "claim-method", "statement": "A bidirectional two-sample Mendelian randomization (MR) investigation was conducted to examine the potential relationship between C1Q and IS.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38179058", "locator": "sections[14] \"Study design and data source\" paragraph 2", "quote": "A bidirectional two-sample Mendelian randomization (MR) investigation was conducted to examine the potential relationship between C1Q and IS."}], "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:38179058", "locator": "sections[31] \"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 results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013–1.234, P = 0.027).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013–1.234, P = 0.027)."}, "evidence": [{"asset": "source:pmid:38179058", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013–1.234, P = 0.027)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013–1.234, P = 0.027).", "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:38179058"], "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:GSE100927"], "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:GSE100927"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38179058", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1289223", "sha256": "sha256:e1ff6dfb1942a752fcf935eddbf4373c018f1fca0b1fe190b394ae3b1651843e", "bytes": 79746, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1289223", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10764496", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100927", "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=GSE100927", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100927", "version": null, "note": "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 .", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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A run that reproduces the effect is judged against this threshold."}], "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": ["mr_estimate"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mendelian_randomisation."}, "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": ["GSE159677", "GSE28829", "GSE43292", "GSE41571", "GSE100927"], "resolved_accessions": ["GSE159677", "GSE28829", "GSE43292", "GSE41571", "GSE100927"], "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 GSE159677, GSE28829, GSE43292, GSE41571, GSE100927 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": ["mr_estimate"], "assets": ["source:pmid:38179058", "data:geo:GSE100927"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE100927"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:04:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 21658, "completion_tokens": 2293, "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:38179058", "type": "paper", "label": "pmid:38179058"}, {"id": "source:pmid:38179058", "type": "manuscript", "label": "PMID 38179058 full text"}, {"id": "data:geo:GSE100927", "type": "dataset", "label": "GEO GSE100927"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38179058", "type": "paper", "label": "pmid:38179058"}, {"id": "source:pmid:38179058", "type": "manuscript", "label": "PMID 38179058 full text"}, {"id": "data:geo:GSE100927", "type": "dataset", "label": "GEO GSE100927"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38179058", "type": "extraction", "used": ["source:pmid:38179058"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE100927", "type": "accession_resolution", "used": ["data:geo:GSE100927"], "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:38179058", "parent_hash": "sha256:e361e09257af8f6ed1c77d45523373803f4343c32aedeabe74884a2cc817731c", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE100927 licence not read", "asset:data:geo:GSE100927 not downloaded", "asset:data:geo:GSE159677 licence not read", "asset:data:geo:GSE159677 not downloaded", "asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE41571 licence not read", "asset:data:geo:GSE41571 not downloaded", "asset:data:geo:GSE43292 licence not read", "asset:data:geo:GSE43292 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": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization an", "h C1Q associated hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnos"], "order_basis": "paper_text_order:3", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["to establish C1Q associated hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnos", "hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnose and predi", "an randomization (MR) analysis. Methods: HAP scRNA-seq and bulk-RNA data were download from the Gen", "sed as the main method. Results: We utilized scRNA-seq dataset (GSE159677) to identify 24 cell clus"], "order_basis": "paper_text_order:314", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["RAW264.7 macrophages and apoE-/- mice using qPCR. The results of MR indicated that there was"], "order_basis": "paper_text_order:2093", "id": "assay:3"}, {"role": "analysis", "definition_id": "genetic_association", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["mr_estimate"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["A bidirectional two-sample Mendelian randomization (MR) investigation was conducted to examine the potential relationship between C1Q and IS."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}