Identification of the feature genes involved in cytokine release syndrome in COVID-19.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38165854", "kind": "science-record", "revision": 4, "content_hash": "sha256:2498f9795951bab51c254209a5ef4b9519bfe4aacf53c7e7b9539a8dcf150a1c", "created_at": "2026-11-01T19:20:05Z", "updated_at": "2026-11-01T22:53:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of the feature genes involved in cytokine release syndrome in COVID-19.", "doi": "10.1371/journal.pone.0296030", "pmid": "38165854", "authors": ["Bing Yang", "Meijun Pan", "Kai Feng", "Xue Wu", "Fang Yang", "Peng Yang"], "journal": "PloS one", "year": 2024, "abstract": "OBJECTIVE: Screening of feature genes involved in cytokine release syndrome (CRS) from the coronavirus disease 19 (COVID-19).\nMETHODS: The data sets related to COVID-19 were retrieved using Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) related to CRS were analyzed with R software and Venn diagram, and the biological processes and signaling pathways involved in DEGs were analyzed with GO and KEGG enrichment. Core genes were screened using Betweenness and MCC algorithms. GSE164805 and GSE171110 dataset were used to verify the expression level of core genes. Immunoinfiltration analysis was performed by ssGSEA algorithm in the GSVA package. The DrugBank database was used to analyze the feature genes for potential therapeutic drugs.\nRESULTS: This study obtained 6950 DEGs, of which 971 corresponded with CRS disease genes (common genes). GO and KEGG enrichment showed that multiple biological processes and signaling pathways associated with common genes were closely related to the inflammatory response. Furthermore, the analysis revealed that transcription factors that regulate these common genes are also involved in inflammatory response. Betweenness and MCC algorithms were used for common gene screening, yielding seven key genes. GSE164805 and GSE171110 dataset validation revealed significant differences between the COVID-19 and normal controls in four core genes (feature genes), namely IL6R, TLR4, TLR2, and IFNG. The upregulated IL6R, TLR4, and TLR2 genes were mainly involved in the Toll-like receptor signaling pathway of the inflammatory pathway, while the downregulated IFNG genes primarily participated in the necroptosis and JAK-STAT signaling pathways. Moreover, immune infiltration analysis indicated that higher expression of these genes was associated with immune cell infiltration that mediates inflammatory response. In addition, potential therapeutic drugs for these four feature genes were identified via the DrugBank database.\nCONCLUSION: IL6R, TLR4, TLR2, and IFNG may be potential pathogenic genes and therapeutic targets for the CRS associated with COVID-19.", "claims": [{"id": "claim-method", "statement": "The DEGs were screened using the Limma package (version 3.57.7) and #dplyr package (version 1.1.2), and the code is listed in S4 in S1 Method, with P<0.05 and |LogFC|>1 as conditions [15, 16].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38165854", "locator": "sections[4] \"Analysis of the differential expression genes (DEGs)\" paragraph 2", "quote": "The DEGs were screened using the Limma package (version 3.57.7) and #dplyr package (version 1.1.2), and the code is listed in S4 in S1 Method, with P<0.05 and |LogFC|>1 as conditions [15, 16]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38165854", "locator": "sections[12] \"Analysis of the COVID-19 and healthy DEGs\" paragraph 2", "quote": "Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset."}], "state": "complete"}, {"id": "claim-target-result", "statement": "IL6R, TLR4, TLR2, and IFNG may be potential pathogenic genes and therapeutic targets for the CRS associated with COVID-19.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38165854", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "IL6R, TLR4, TLR2, and IFNG may be potential pathogenic genes and therapeutic targets for the CRS associated with COVID-19."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "IL6R, TLR4, TLR2, and IFNG may be potential pathogenic genes and therapeutic targets for the CRS associated with COVID-19.", "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:38165854"], "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:GSE164805"], "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:GSE164805"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38165854", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0296030", "sha256": "sha256:353daeef7de5a398ee6c60432a3d09229700d417a7e75d1f80a49b6bdb95fc5a", "bytes": 27188, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0296030", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10760774", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE164805", "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=GSE164805", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE164805", "version": null, "note": "Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM5019817", "GSM5019818", "GSM5019819", "GSM5019820", "GSM5019821", "GSM5019822", "GSM5019823", "GSM5019824", "GSM5019825", "GSM5019826", "GSM5019827", "GSM5019828", "GSM5019829", "GSM5019830", "GSM5019831"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "26963", "taxon": "Homo sapiens", "title": "The transcriptional profiles of severe COVID-19", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE171110", "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=GSE171110", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE171110", "version": null, "note": "Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM5218990", "GSM5218991", "GSM5218992", "GSM5218993", "GSM5218994", "GSM5218995", "GSM5218996", "GSM5218997", "GSM5218998", "GSM5218999", "GSM5219000", "GSM5219001", "GSM5219002", "GSM5219003", "GSM5219004", "GSM5219005", "GSM5219006", "GSM5219007", "GSM5219008", "GSM5219009", "GSM5219010", "GSM5219011", "GSM5219012", "GSM5219013", "GSM5219014", "GSM5219015", "GSM5219016", "GSM5219017", "GSM5219018", "GSM5219019", "GSM5219020", "GSM5219021", "GSM5219022", "GSM5219023", "GSM5219024", "GSM5219025", "GSM5219026", "GSM5219027", "GSM5219028", "GSM5219029", "GSM5219030", "GSM5219031", "GSM5219032", "GSM5219033", "GSM5219034", "GSM5219035", "GSM5219036", "GSM5219037", "GSM5219038", "GSM5219039", "GSM5219040", "GSM5219041", "GSM5219042", "GSM5219043"], "sample_count": 54, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Whole blood transciptome analysis in severe Covid-19  patients and healthy donors", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE164805 not downloaded", "asset:data:geo:GSE164805 licence not read", "asset:data:geo:GSE171110 not downloaded", "asset:data:geo:GSE171110 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": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The DEGs were screened using the Limma package (version 3.57.7) and #dplyr package (version 1.1.2), and the code is listed in S4 in S1 Method, with P<0.05 and |LogFC|>1 as conditions [15, 16]."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "Principal Component Analysis"}}, {"id": "method-4", "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": 0.8, "band": "high", "quote": "PPI"}}], "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": ["GSE164805", "GSE171110"], "resolved_accessions": ["GSE164805", "GSE171110"], "statements": ["Comprehensive gene expression information was obtained from 10 COVID-19 patients and five Healthy controls in the GSE164805 dataset."], "basis": "The paper names GSE164805, GSE171110 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:38165854", "data:geo:GSE164805"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE164805"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:04:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 8086, "completion_tokens": 2267, "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:38165854", "type": "paper", "label": "pmid:38165854"}, {"id": "source:pmid:38165854", "type": "manuscript", "label": "PMID 38165854 full text"}, {"id": "data:geo:GSE164805", "type": "dataset", "label": "GEO GSE164805"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38165854", "type": "paper", "label": "pmid:38165854"}, {"id": "source:pmid:38165854", "type": "manuscript", "label": "PMID 38165854 full text"}, {"id": "data:geo:GSE164805", "type": "dataset", "label": "GEO GSE164805"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38165854", "type": "extraction", "used": ["source:pmid:38165854"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE164805", "type": "accession_resolution", "used": ["data:geo:GSE164805"], "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:38165854", "parent_hash": "sha256:5ffe14da9088b57ebdbf134fda22fc6f3552b1afdccffee4770243c8b8b20879", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE164805 licence not read", "asset:data:geo:GSE164805 not downloaded", "asset:data:geo:GSE171110 licence not read", "asset:data:geo:GSE171110 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 DEGs were screened using the Limma package (version 3.57.7) and #dplyr package (version 1.1.2), and the code is listed in S4 in S1 Method, with P<0.05 and |LogFC|>1 as conditions [15, 16]."], "order_basis": "analysis_only", "id": "assay:1"}]}