Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Cytokine Pathways Involved in COVID-19 After Rhinovirus Infection in Asthma Patients.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33315853", "kind": "science-record", "revision": 9, "content_hash": "sha256:66a1cc807285a411e49bbe40044b77a62a1574593bbbe8c4fe3d351a5329f639", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:45:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Cytokine Pathways Involved in COVID-19 After Rhinovirus Infection in Asthma Patients.", "doi": "10.12659/MSM.928861", "pmid": "33315853", "authors": ["Wenjuan Dai", "Dawei Cao", "Wei Zhang", "Yangyang Wei", "Daqing Ding", "Bei Li", "Yan Gao", "Lixuan Zhao", "Yi Jiang", "Xiaomei Kong"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2020, "abstract": "BACKGROUND Rhinovirus (RV) is the most common pathogen involved in asthma, and COVID-19, caused by SARS-COV-2, may be more severe in asthma patients. Here, we applied integrated bioinformatics to identify potential key genes and cytokine pathways after RV infection in asthma, and analyzed changes in angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-COV-2. MATERIAL AND METHODS The gene expression profile dataset GSE149273 was downloaded from NCBI-GEO, which included 90 samples of non-infected, RVA, and RVC. Differentially expressed genes (DEGs) were identified using t tests in the limma R package, and subsequently investigated by GO, KEGG, and DO analysis. Moreover, the expression of ACE2 and the proportion of immune cells were further analyzed to determine the effects of RV on cytokines. RESULTS A total of 555 DEGs of RVA and 421 of RVC were identified. There were 415 DEGs in RVA and RVC, of which 406 were upregulated and 9 were downregulated. The functional enrichment analysis showed that most DEGs were obviously enriched in cytokines, and were mainly enriched in \"influenza\" and \"hepatitis C, chronic\". In addition, the expression of ACE2 increased significantly and the proportion of immune cytokines significantly changed after RV infection. Our results suggest that RV can activate the cytokine pathway associated with COVID-19 by increasing ACE2. CONCLUSIONS The DEGs and related cytokine pathways after asthma RV infection identified using integrated bioinformatics in this study elucidate the potential link between RV and COVID-19.", "claims": [{"id": "claim-method", "statement": "The t test method in the limma R package was subsequently used to identify DEGs between RVA and RVC infected samples and non-infected samples, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33315853", "locator": "sections[4] \"Expression analysis of DEGs\" paragraph 2", "quote": "The t test method in the limma R package was subsequently used to identify DEGs between RVA and RVC infected samples and non-infected samples, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE149273 profile dataset was downloaded from the NCBI-GEO database (https://www.ncbi.nlm.nih.gov/geo/). The platform for GSE149273 is GPL21290 Illumina HiSeq 3000 (Homo sapiens), which includes 90 samples from 30 asthma patients with non-infection, RVA, and RVC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33315853", "locator": "sections[3] \"Dataset sources\" paragraph 2", "quote": "The GSE149273 profile dataset was downloaded from the NCBI-GEO database (https://www.ncbi.nlm.nih.gov/geo/). The platform for GSE149273 is GPL21290 Illumina HiSeq 3000 (Homo sapiens), which includes 90 samples from 30 asthma patients with non-infection, RVA, and RVC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33315853"], "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:GSE149273"], "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:GSE149273"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33315853", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.928861", "sha256": "sha256:4d8184b6c29d993758f8cf30f250c3ba74d3a2df558224c97949b79b3efffb6f", "bytes": 29375, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.12659/MSM.928861", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7747473", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE149273", "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=GSE149273", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE149273", "version": null, "note": "The GSE149273 profile dataset was downloaded from the NCBI-GEO database (https://www.ncbi.nlm.nih.gov/geo/). 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"media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b44e9801b94bbbb0e1ab25a32151d60f7081db8282ab339a6a12a72f273fd9d0", "bytes": 3355, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#t1-medscimonit-26-e928861", "version": null, "note": "415 DEGs in the intersection of FVA and FVC.", "structure": {"pmcid": "PMC7747473", "section_index": 8, "section_title": "Data information and identification of DEGs", "row_count": 3, "column_count": 2}, "table": {"label": "Table 1", "caption": "415 DEGs in the intersection of FVA and FVC.", "rows": [["DEGs", "Genes"], ["Upregulated", "IRF7, MX2, CMPK2, TRIM25, OAS3, IFIT5, DDX60L, RSAD2, MX1, IFI16, ADAR, USP18, STAT1, PNPT1, TRIM14, OAS1, OAS2, XAF1, IFIT1, DHX58, DDX58, CMTR1, RTP4, PARP12, SP100, EPSTI1, IFIT2, PARP9, IFI35, HERC6, LAMP3, UBE2L6, SAMD9L, PLSCR1, HERC5, OASL, IFIT3, C19orf66, IFI44, TRANK1, SP110, HSH2D, DTX3L, ISG15, 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OGFR, LYPD5, APOBEC3A, IFNL1, AKAP7, ACKR4, TNFAIP3, RBMS2, HESX1, HTR2B, MXD1, IL4I1, BLZF1, DUOXA2, NCOA7, RBM11, HRASLS2, SUSD3, FGD2, CCL5, IFI27, TICAM1, CCDC109B, APOBEC3F, GCH1, IL22RA1, TNFSF13B, C19orf38, IKBKE, IFNL2, CASP10, LRRN2, PPM1K, CD7, APOL3, IRAK2, NFKBIZ, UBQLNL, C21orf91, IL7, HLA-F, CD38, RELB, GCNT4, RHBDF2, CX3CL1, CD83, TNFRSF6B, PPM1J, TAGAP, BTN3A3, TMEM229B, FFAR2, CARD16, SOCS1, STX11, OVOL1, IL19, BIRC3, GLRX, CPNE5, MAFF, CXorf49, CXorf49B, CEACAM1, SEC16B, PRDM1, ADCY4, ATF3, LINC00623, TLR2, IFITM2, NRG2, BBC3, SOCS3, KIAA0226, CXCL11, CXCL9, IL15RA, LAG3, STARD4, IDO1, SOCS2, ICOSLG, C1GALT1, FANCA, KCNQ4, NCF1, C10orf105, AP5B1, TMEM171, GBP2, HK2, BRIP1, RAB43, MUC13, IFI30, NCF1C, SP140, HAPLN3, ARID5A, SLC16A1, CD274, KLHDC7B, CACNA1A, CSF3, MAP2, CCL20, TMEM106A, SERPING1, TNFAIP2, CLCA3P, TNIP3, DLG2, CXCL8, MAPK8IP2, IL17C, PLAUR, NEURL3, PROX1, APOBEC3B, TNF, MB21D1, THEMIS2, FRMD3, HBEGF, BRCA2, DUXAP10, TMEM92, DUSP5, EXOC3L4, APOL4, C11orf82, RIMS2, C15orf48, C2CD4B, NOV, ADAM8, SLFN12, MICB, GBP3, GRIN3A, C1R, LOC102724163, SEMA3D, IL2RG, LOC645638, FGF2, FAM169B, LOC100294362, MT2A, ABCD1, ZNF618, LRRC3, SAA4, CYP21A1P, SLC26A4-AS1, SERPINB9, SERPINB9P1, BATF, LOC388692, TLDC2, IL36G, PRRX2, TGM1, ELOVL7, CXCL3, TNFRSF10A, RTKN2, CCL22, HDAC9, ATP10A, IL6, SBK1, BCL2A1, DOC2B, C2CD4A, C1S, ADM, HCG4B, PTPRH, HCAR3, PDCD1LG2, C8orf4, CXCL2, STS, RET, NOS2, SLC26A4, SLCO4A1, SELL, NTNG2, HLA-J, RND1, CFB, XDH, MMP13, TRIM31, SAA2, SPRR2A, PTGS2, MTNR1A, AKAP2, ACHE, DEFB4A, ICAM1, EREG, SPRR2F, CH25H, IL1RN, NEXN, CSF1, HSPA6, LOC554223, APOL1, SLAMF7, LIF, MEF2C, SSC5D, TGM2, ZDHHC14, CXCL13, ERAP2, ANGPTL4, SH2D1B, THSD1, PLA2G4E"], ["Downregulated", "C20orf195, FAM13C, HPX, INHBB, GPATCH11, PTGFR, PRR18, SLC16A14, SLC47A2"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[8]/table-wrap[1]#t1-medscimonit-26-e928861"}}, {"id": "asset:table:pmid:33315853:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:08cc4c06ea5d4eed0f58bfce0058233eed081ed3837bccebe807f8a351ef1212", "bytes": 1637, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#t2-medscimonit-26-e928861", "version": null, "note": "GO functional annotation for the most significantly related targets of 415 DEGs.", "structure": {"pmcid": "PMC7747473", "section_index": 9, "section_title": "Functional enrichment analysis", "row_count": 23, "column_count": 4}, "table": {"label": "Table 2", "caption": "GO functional annotation for the most significantly related targets of 415 DEGs.", "rows": [["GO ID", "GO Term", "Count", "P-value"], ["BP"], ["GO: 0009615", "Response to virus", "75", "9.27E-60"], ["GO: 0051607", "Defense response to virus", "67", "1.20E-59"], ["GO: 0034341", "Response to interferon-gamma", "51", "5.09E-43"], ["GO: 0060337", "Type I interferon signaling pathway", "38", "1.25E-40"], ["GO: 0071357", "Cellular response to type i interferon", "38", "1.25E-40"], ["GO: 0034340", "Response to type i interferon", "38", "8.46E-40"], ["GO: 0071346", "Cellular response to interferon-gamma", "45", "1.81E-37"], ["GO: 0048525", "Negative regulation of viral process", "33", "2.80E-32"], ["GO: 0060333", "Interferon-gamma-mediated signaling pathway", "32", "3.39E-32"], ["GO: 1903901", "Negative regulation of viral life cycle", "31", "8.43E-32"], ["MF"], ["GO: 0005125", "Cytokine activity", "29", "1.03E-15"], ["GO: 0048018", "Receptor ligand activity", "39", "1.62E-13"], ["GO: 0005126", "Cytokine receptor binding", "29", "9.81E-13"], ["GO: 0042379", "Chemokine receptor binding", "13", "5.95E-10"], ["GO: 0008009", "Chemokine activity", "11", "2.92E-09"], ["GO: 0045236", "CXCR chemokine receptor binding", "6", "2.79E-08"], ["GO: 0003725", "Double-stranded RNA binding", "12", "3.25E-08"], ["GO: 0016814", "Hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines", "7", "4.39E-06"], ["GO: 0042056", "Chemoattractant activity", "7", "9.61E-06"], ["GO: 0048020", "CCR chemokine receptor binding", "7", "2.25E-05"]], "row_count": 23, "column_count": 4, "numeric_cells": 60, "header_rows": 1, "locator": "section[9]/table-wrap[1]#t2-medscimonit-26-e928861"}}, {"id": "asset:table:pmid:33315853:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1ab9fe2c14fc59367c9c193f87f770f3faae42816742f246a401aae46d3242d7", "bytes": 2121, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[2]#t3-medscimonit-26-e928861", "version": null, "note": "KEGG functional annotation for 415 DEGs.", "structure": {"pmcid": "PMC7747473", "section_index": 9, "section_title": "Functional enrichment analysis", "row_count": 33, "column_count": 4}, "table": {"label": "Table 3", "caption": "KEGG functional annotation for 415 DEGs.", "rows": [["KEGG ID", "KEGG Term", "Count", "P-value"], ["hsa05164", "Influenza A", "33", "4.44E-20"], ["hsa04621", "NOD-like receptor signaling pathway", "30", "2.20E-16"], ["hsa04060", "Cytokine-cytokine receptor interaction", "34", "1.28E-13"], ["hsa04061", "Viral protein interaction with cytokine and cytokine receptor", "20", "7.62E-13"], ["hsa04668", "TNF signaling pathway", "20", "7.04E-12"], ["hsa05162", "Measles", "22", "7.43E-12"], ["hsa05169", "Epstein-Barr virus infection", "24", "3.95E-10"], ["hsa05160", "Hepatitis C", "20", "3.30E-09"], ["hsa04064", "NF-kappa B signaling pathway", "16", "9.32E-09"], ["hsa04657", "IL-17 signaling pathway", "15", "1.65E-08"], ["hsa05167", "Kaposi sarcoma-associated herpesvirus infection", "21", "1.77E-08"], ["hsa04630", "JAK-STAT signaling pathway", "19", "3.65E-08"], ["hsa04623", "Cytosolic DNA-sensing pathway", "12", "6.12E-08"], ["hsa04620", "Toll-like receptor signaling pathway", "15", "6.73E-08"], ["hsa04622", "RIG-I-like receptor signaling pathway", "12", "2.08E-07"], ["hsa04625", "C-type lectin receptor signaling pathway", "14", "4.49E-07"], ["hsa04217", "Necroptosis", "17", "7.52E-07"], ["hsa05134", "Legionellosis", "10", "1.77E-06"], ["hsa04062", "Chemokine signaling pathway", "18", "1.94E-06"], ["hsa05133", "Pertussis", "11", "3.86E-06"], ["hsa05161", "Hepatitis B", "16", "4.60E-06"], ["hsa05168", "Herpes simplex virus 1 infection", "29", "2.77E-05"], ["hsa05323", "Rheumatoid arthritis", "11", "2.78E-05"], ["hsa05170", "Human immunodeficiency virus 1 infection", "16", "0.000129"], ["hsa05145", "Toxoplasmosis", "11", "0.000155"], ["hsa05140", "Leishmaniasis", "9", "0.000166"], ["hsa05144", "Malaria", "7", "0.000289"], ["hsa05143", "African trypanosomiasis", "6", "0.00035"], ["hsa05235", "PD-L1 expression and PD-1 checkpoint pathway in cancer", "9", "0.000498"], ["hsa04612", "Antigen processing and presentation", "8", "0.000928"], ["hsa04930", 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"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": ["GSE149273"], "resolved_accessions": ["GSE149273"], "statements": ["The GSE149273 profile dataset was downloaded from the NCBI-GEO database (https://www.ncbi.nlm.nih.gov/geo/). The platform for GSE149273 is GPL21290 Illumina HiSeq 3000 (Homo sapiens), which includes 90 samples from 30 asthma patients with non-infection, RVA, and RVC."], "basis": "The paper names GSE149273 in NCBI-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:33315853", "data:geo:GSE149273", "asset:table:pmid:33315853:1", "asset:table:pmid:33315853:2", "asset:table:pmid:33315853:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE149273"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:02Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 23250, "completion_tokens": 847, "cached_tokens": 520}}, "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:33315853", "type": "paper", "label": "pmid:33315853"}, {"id": "source:pmid:33315853", "type": "manuscript", "label": "PMID 33315853 full text"}, {"id": "data:geo:GSE149273", "type": "dataset", "label": "GEO GSE149273"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33315853", "type": "paper", "label": "pmid:33315853"}, {"id": "source:pmid:33315853", "type": "manuscript", "label": "PMID 33315853 full text"}, {"id": "data:geo:GSE149273", "type": "dataset", "label": "GEO GSE149273"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33315853", "type": "extraction", "used": ["source:pmid:33315853"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE149273", "type": "accession_resolution", "used": ["data:geo:GSE149273"], "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:33315853", "parent_hash": "sha256:1df1c969fb3fe526f7f341755d354d990904ccde3b33fab7178d30fefd095f97", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE149273 licence not read", "asset:data:geo:GSE149273 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": 1.0, "evidence": ["The t test method in the limma R package was subsequently used to identify DEGs between RVA and RVC infected samples and non-infected samples, respectively."], "order_basis": "analysis_only", "id": "assay:1"}]}