Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35187081", "kind": "science-record", "revision": 5, "content_hash": "sha256:2d6fa757f816325c223a30e3a96024b2ffcb8d1fc80791fb42ca854c815c0b26", "created_at": "2026-11-01T17:36:57Z", "updated_at": "2026-11-01T22:48:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis.", "doi": "10.3389/fmolb.2022.805570", "pmid": "35187081", "authors": ["Gongqi Chen", "Dian Chen", "Yuchen Feng", "Wenliang Wu", "Jiali Gao", "Chenli Chang", "Shengchong Chen", "Guohua Zhen"], "journal": "Frontiers in molecular biosciences", "year": 2022, "abstract": "Background: Asthma is a heterogeneous disease with different subtypes including eosinophilic asthma (EA) and neutrophilic asthma (NA). However, the mechanisms underlying the difference between the two subtypes are not fully understood. Methods: Microarray datasets (GSE45111 and GSE137268) were acquired from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in induced sputum between EA (n = 24) and NA (n = 15) were identified by \"Limma\" package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Gene set enrichment analysis (GSEA) were used to explore potential signaling pathways. Weighted gene co-expression network analysis (WGCNA) were performed to identify the key genes that were strongly associated with EA and NA. Results: A total of 282 DEGs were identified in induced sputum of NA patients compared with EA patients. In GO and KEGG pathway analyses, DEGs were enriched in positive regulation of cytokine production, and cytokine-cytokine receptor interaction. The results of GSEA showed that ribosome, Parkinson's disease, and oxidative phosphorylation were positively correlated with EA while toll-like receptor signaling pathway, primary immunodeficiency, and NOD-like receptor signaling pathway were positively correlated with NA. Using WGCNA analysis, we identified a set of genes significantly associated NA including IRFG, IRF1, STAT1, IFIH1, IFIT3, GBP1, GBP5, IFIT2, CXCL9, and CXCL11. Conclusion: We identified potential signaling pathways and key genes involved in the pathogenesis of the asthma subsets, especially in neutrophilic asthma.", "claims": [{"id": "claim-method", "statement": "We next identified DEGs between EA and NA group by an empirical Bayes method based on limma package (version 3.46.0) in R software (p < 0.05, |logFC|>0.5) (Ritchie et al., 2015).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35187081", "locator": "sections[4] \"Data Processing and Differentially Expressed Genes Identification\" paragraph 2", "quote": "We next identified DEGs between EA and NA group by an empirical Bayes method based on limma package (version 3.46.0) in R software (p < 0.05, |logFC|>0.5) (Ritchie et al., 2015)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35187081", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 282 differentially expressed genes between eosinophilic asthma and neutrophilic asthma induced sputum samples, including 110 up-regulated and 172 down-regulated in eosinophilic asthma.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "After data consolidation and removing the batch effects of the two microarray datasets, 282 DEGs (110 up-regulated and 172 down-regulated in EA patients) were screened out using the Limma package (p < 0.05, |logFC| > 0.5) (Supplementary Table S1)."}, "evidence": [{"asset": "source:pmid:35187081", "locator": "sections[10] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "After data consolidation and removing the batch effects of the two microarray datasets, 282 DEGs (110 up-regulated and 172 down-regulated in EA patients) were screened out using the Limma package (p < 0.05, |logFC| > 0.5) (Supplementary Table S1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 282 differentially expressed genes between eosinophilic asthma and neutrophilic asthma induced sputum samples, including 110 up-regulated and 172 down-regulated in eosinophilic asthma.", "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:35187081"], "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:GSE137268"], "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:GSE137268"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35187081", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2022.805570", "sha256": "sha256:ce1f5515b373aade8c2796bc287c097a586815626192bdec9b977e4092d2eda7", "bytes": 47158, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2022.805570", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8847715", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE137268", "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=GSE137268", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE137268", "version": null, "note": "The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4074168", "GSM4074169", "GSM4074170", "GSM4074171", "GSM4074172", "GSM4074173", "GSM4074174", "GSM4074175", "GSM4074176", "GSM4074177", "GSM4074178", "GSM4074179", "GSM4074180", "GSM4074181", "GSM4074182", "GSM4074183", "GSM4074184", "GSM4074185", "GSM4074186", "GSM4074187", "GSM4074188", "GSM4074189", "GSM4074190", "GSM4074191", "GSM4074192", "GSM4074193", "GSM4074194", "GSM4074195", "GSM4074196", "GSM4074197", "GSM4074198", "GSM4074199", "GSM4074200", "GSM4074201", "GSM4074202", "GSM4074203", "GSM4074204", "GSM4074205", "GSM4074206", "GSM4074207", "GSM4074208", "GSM4074209", "GSM4074210", "GSM4074211", "GSM4074212", "GSM4074213", "GSM4074214", "GSM4074215", "GSM4074216", "GSM4074217", "GSM4074218", "GSM4074219", "GSM4074220", "GSM4074221", "GSM4074222", "GSM4074223", "GSM4074224", "GSM4074225", "GSM4074226", "GSM4074227", "GSM4074228", "GSM4074229", "GSM4074230", "GSM4074231", "GSM4074232", "GSM4074233", "GSM4074234", "GSM4074235", "GSM4074236"], "sample_count": 69, "group_sizes": null, "group_sizes_basis": null, "platform": "6104", "taxon": "Homo sapiens", "title": "Transcriptomic analysis of induced sputum samples in severe asthma", "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:GSE45111", "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=GSE45111", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE45111", "version": null, "note": "The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1096929", "GSM1096930", "GSM1096931", "GSM1096932", "GSM1096933", "GSM1096934", "GSM1096935", "GSM1096936", "GSM1096937", "GSM1096938", "GSM1096939", "GSM1096940", "GSM1096941", "GSM1096942", "GSM1096943", "GSM1096944", "GSM1096945", "GSM1096946", "GSM1096947", "GSM1096948", "GSM1096949", "GSM1096950", "GSM1096951", "GSM1096952", "GSM1096953", "GSM1096954", "GSM1096955", "GSM1096956", "GSM1096957", "GSM1096958", "GSM1096959", "GSM1096960", "GSM1096961", "GSM1096962", "GSM1096963", "GSM1096964", "GSM1096965", "GSM1096966", "GSM1096967", "GSM1096968", "GSM1096969", "GSM1096970", "GSM1096971", "GSM1096972", "GSM1096973", "GSM1096974", "GSM1096975"], "sample_count": 47, "group_sizes": null, "group_sizes_basis": null, "platform": "6104", "taxon": "Homo sapiens", "title": "A sputum gene expression signature of six biomarkers identifies asthma inflammatory phenotype and steroid responsiveness", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE137268 not downloaded", "asset:data:geo:GSE137268 licence not read", "asset:data:geo:GSE45111 not downloaded", "asset:data:geo:GSE45111 licence not read"]}, "analysis": {"state": "complete", "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": "We next identified DEGs between EA and NA group by an empirical Bayes method based on limma package (version 3.46.0) in R software (p < 0.05, |logFC|>0.5) (Ritchie et al., 2015)."}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "differential_expression_fit", "expected_value": 0.05, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": ["GSE45111", "GSE137268"], "resolved_accessions": ["GSE45111", "GSE137268"], "statements": ["The datasets analyzed during the present study are available from the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45111 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137268)."], "basis": "The paper names GSE45111, GSE137268 in Gene Expression Omnibus 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:35187081", "data:geo:GSE137268"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE137268"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:35:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14960, "completion_tokens": 1362, "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:35187081", "type": "paper", "label": "pmid:35187081"}, {"id": "source:pmid:35187081", "type": "manuscript", "label": "PMID 35187081 full text"}, {"id": "data:geo:GSE137268", "type": "dataset", "label": "GEO GSE137268"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35187081", "type": "paper", "label": "pmid:35187081"}, {"id": "source:pmid:35187081", "type": "manuscript", "label": "PMID 35187081 full text"}, {"id": "data:geo:GSE137268", "type": "dataset", "label": "GEO GSE137268"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35187081", "type": "extraction", "used": ["source:pmid:35187081"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE137268", "type": "accession_resolution", "used": ["data:geo:GSE137268"], "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:35187081", "parent_hash": "sha256:3af5f05aefa74f3e7e71ff1782c9591a9760e79bfc50822728b6ce5d74b02de0", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE137268 licence not read", "asset:data:geo:GSE137268 not downloaded", "asset:data:geo:GSE45111 licence not read", "asset:data:geo:GSE45111 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["subtypes are not fully understood. Methods: Microarray datasets (GSE45111 and GSE137268) were acqui"], "order_basis": "paper_text_order:348", "id": "assay:1"}, {"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": ["We next identified DEGs between EA and NA group by an empirical Bayes method based on limma package (version 3.46.0) in R software (p < 0.05, |logFC|>0.5) (Ritchie et al., 2015)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}