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pmid:38854719
Weighted gene co-expression network analysis and whole genome sequencing identify potential lung cancer biomarkers.
Mireguli Abudereheman · Zhengjun Lian · Baidurula Ainitu
Frontiers in oncology · 2024 doi:10.3389/fonc.2024.1355527
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Experiment
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Analysis
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Complete file
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We constructed gene co-expression networks and carried out whole-exome sequencing (WES) to identify key modules, hub genes, and the most recurrently mutated genes involved in the pathogenesis of TB-associated LC.\nMethods: The data used in this study were obtained from the Gene Expression Omnibus (GEO) and WES. First, we screened LC-related genes in GSE43458 and TB-related genes in GSE83456 by weighted gene co-expression network analysis (WGCNA). Subsequently, we screened differentially expressed genes related to LC and TB in GSE42834. We also performed WES of 15 patients (TB, n = 5; LC, n = 5; TB+LC, n = 5), constructed mutational profiles, and identified differences in the profiles of the three groups for further investigation.\nResults: We identified 278 hub genes associated with tumorigenesis of pulmonary TB. Moreover, WES identified 112 somatic mutations in 25 genes in the 15 patients. Finally, four common genes (EGFR, HSPA2, CECR2, and LAMA3) were confirmed in a Venn diagram of the 278 hub genes and the mutated genes from WES. KEGG analysis revealed various pathway changes. The PI3K-AKT signaling pathway was the most enriched pathway, and all four genes are included in this pathway. Thus, these four genes and the PI3K-AKT signaling pathway may play important roles in LC.\nConclusion: Several potential genes and pathways related to TB-associated LC were identified, including EGFR and three target genes not found in previous studies. These genes are related to cell proliferation, colony formation, migration, and invasion, and provide a direction for future research into the mechanisms of LC co-occurring with TB. The PI3K-AKT signaling pathway was also identified as a potential key pathway involved in LC development.", "claims": [{"id": "claim-method", "statement": "First, we screened LC-related genes in GSE43458 and TB-related genes in GSE83456 by weighted gene co-expression network analysis (WGCNA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38854719", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "First, we screened LC-related genes in GSE43458 and TB-related genes in GSE83456 by weighted gene co-expression network analysis (WGCNA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the GEO database (ID: GSE43458, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43458; GSE83456, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456; GSE42834, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42834. 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The WES datasets used and/or analyzed during the current study are available from the BioProject database (BioProject ID: PRJNA1080061; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1080061)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Four common genes—EGFR, HSPA2, CECR2, and LAMA3—were identified at the intersection of 278 hub genes and genes mutated by WES.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38854719", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Finally, four common genes (EGFR, HSPA2, CECR2, and LAMA3) were confirmed in a Venn diagram of the 278 hub genes and the mutated genes from WES."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Four common genes—EGFR, HSPA2, CECR2, and LAMA3—were identified at the intersection of 278 hub genes and genes mutated by WES.", "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:38854719"], "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:GSE42834"], "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:GSE42834"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38854719", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2024.1355527", "sha256": "sha256:477842ab61b533e49f54b263e2b1ad279e64e00e56750142852295174aa25e8d", "bytes": 31270, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2024.1355527", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11157001", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE42834", "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=GSE42834", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE42834", "version": null, "note": "The datasets used and/or analyzed during the current study are available from the GEO database (ID: GSE43458, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43458; GSE83456, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456; GSE42834, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42834. 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The WES datasets used and/or analyzed during the current study are available from the BioProject database (BioProject ID: PRJNA1080061; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1080061).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed during the current study are available from the GEO database (ID: GSE43458, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43458; GSE83456, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456; GSE42834, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42834. The WES datasets used and/or analyzed during the current study are available from the BioProject database (BioProject ID: PRJNA1080061; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1080061).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2203540", "GSM2203541", "GSM2203542", "GSM2203543", "GSM2203544", "GSM2203545", "GSM2203546", "GSM2203547", "GSM2203548", "GSM2203549", "GSM2203550", "GSM2203551", "GSM2203552", "GSM2203553", "GSM2203554", "GSM2203555", "GSM2203556", "GSM2203557", "GSM2203558", "GSM2203559", "GSM2203560", "GSM2203561", "GSM2203562", "GSM2203563", "GSM2203564", "GSM2203565", "GSM2203566", "GSM2203567", "GSM2203568", "GSM2203569", "GSM2203570", "GSM2203571", "GSM2203572", "GSM2203573", "GSM2203574", "GSM2203575", "GSM2203576", "GSM2203577", "GSM2203578", "GSM2203579", "GSM2203580", "GSM2203581", "GSM2203582", "GSM2203583", "GSM2203584", "GSM2203585", "GSM2203586", "GSM2203587", "GSM2203588", "GSM2203589", "GSM2203590", "GSM2203591", "GSM2203592", "GSM2203593", "GSM2203594", "GSM2203595", "GSM2203596", "GSM2203597", "GSM2203598", "GSM2203599", "GSM2203600", "GSM2203601", "GSM2203602", "GSM2203603", "GSM2203604", "GSM2203605", "GSM2203606", "GSM2203607", "GSM2203608", "GSM2203609", "GSM2203610", "GSM2203611", "GSM2203612", "GSM2203613", "GSM2203614", "GSM2203615", "GSM2203616", "GSM2203617", "GSM2203618", "GSM2203619", "GSM2203620", "GSM2203621", "GSM2203622", "GSM2203623", "GSM2203624", "GSM2203625", "GSM2203626", "GSM2203627", "GSM2203628", "GSM2203629", "GSM2203630", "GSM2203631", "GSM2203632", "GSM2203633", "GSM2203634", "GSM2203635", "GSM2203636", "GSM2203637", "GSM2203638", "GSM2203639", "GSM2203640", "GSM2203641", "GSM2203642", "GSM2203643", "GSM2203644", "GSM2203645", "GSM2203646", "GSM2203647", "GSM2203648", "GSM2203649", "GSM2203650", "GSM2203651", "GSM2203652", "GSM2203653", "GSM2203654", "GSM2203655", "GSM2203656", "GSM2203657", "GSM2203658", "GSM2203659", "GSM2203660", "GSM2203661", "GSM2203662", "GSM2203663", "GSM2203664", "GSM2203665", "GSM2203666", "GSM2203667", "GSM2203668", "GSM2203669", "GSM2203670", "GSM2203671", "GSM2203672", "GSM2203673", "GSM2203674", "GSM2203675", "GSM2203676", "GSM2203677", "GSM2203678", "GSM2203679", "GSM2203680", "GSM2203681", "GSM2203682", "GSM2203683", "GSM2203684", "GSM2203685", "GSM2203686", "GSM2203687", "GSM2203688", "GSM2203689", "GSM2203690", "GSM2203691", "GSM2203692", "GSM2203693", "GSM2203694", "GSM2203695", "GSM2203696", "GSM2203697", "GSM2203698", "GSM2203699", "GSM2203700", "GSM2203701", "GSM2203702", "GSM2203703", "GSM2203704", "GSM2203705", "GSM2203706", "GSM2203707", "GSM2203708", "GSM2203709", "GSM2203710", "GSM2203711", "GSM2203712", "GSM2203713", "GSM2203714", "GSM2203715", "GSM2203716", "GSM2203717", "GSM2203718", "GSM2203719", "GSM2203720", "GSM2203721", "GSM2203722", "GSM2203723", "GSM2203724", "GSM2203725", "GSM2203726", "GSM2203727", "GSM2203728", "GSM2203729", "GSM2203730", "GSM2203731", "GSM2203732", "GSM2203733", "GSM2203734", "GSM2203735", "GSM2203736", "GSM2203737", "GSM2203738", "GSM2203739", "GSM2203740", "GSM2203741"], "sample_count": 202, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PRJNA1080061", "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=PRJNA1080061", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PRJNA1080061", "version": null, "note": "The datasets used and/or analyzed during the current study are available from the GEO database (ID: GSE43458, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43458; GSE83456, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456; GSE42834, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42834. The WES datasets used and/or analyzed during the current study are available from the BioProject database (BioProject ID: PRJNA1080061; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1080061).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed during the current study are available from the GEO database (ID: GSE43458, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43458; GSE83456, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456; GSE42834, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42834. The WES datasets used and/or analyzed during the current study are available from the BioProject database (BioProject ID: PRJNA1080061; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1080061).", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-11-01T20:16:20Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE42834 not downloaded", "asset:data:geo:GSE42834 licence not read", "asset:data:geo:GSE43458 not downloaded", "asset:data:geo:GSE43458 licence not read", "asset:data:geo:GSE83456 not downloaded", "asset:data:geo:GSE83456 licence not read", "asset:data:geo:PRJNA1080061 not downloaded", "asset:data:geo:PRJNA1080061 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-2", "family": null, "specific": null, "label": "weighted gene co-expression network analysis (WGCNA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "First, we screened LC-related genes in GSE43458 and TB-related genes in GSE83456 by weighted gene co-expression network analysis (WGCNA)."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pathway_enrichment."}, "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": ["GSE43458", "GSE83456", "GSE42834", "PRJNA1080061"], "resolved_accessions": ["GSE43458", "GSE83456", "GSE42834"], "statements": ["The datasets used and/or analyzed during the current study are available from the GEO database (ID: GSE43458, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43458; GSE83456, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456; GSE42834, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42834. The WES datasets used and/or analyzed during the current study are available from the BioProject database (BioProject ID: PRJNA1080061; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1080061)."], "basis": "The paper names GSE43458, GSE83456, GSE42834 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pathway_enrich"], "assets": ["source:pmid:38854719", "data:geo:GSE42834"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE42834"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:21:09Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9333, "completion_tokens": 2274, "cached_tokens": 128}}, "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:38854719", "type": "paper", "label": "pmid:38854719"}, {"id": "source:pmid:38854719", "type": "manuscript", "label": "PMID 38854719 full text"}, {"id": "data:geo:GSE42834", "type": "dataset", "label": "GEO GSE42834"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38854719", "type": "paper", "label": "pmid:38854719"}, {"id": "source:pmid:38854719", "type": "manuscript", "label": "PMID 38854719 full text"}, {"id": "data:geo:GSE42834", "type": "dataset", "label": "GEO GSE42834"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38854719", "type": "extraction", "used": ["source:pmid:38854719"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE42834", "type": "accession_resolution", "used": ["data:geo:GSE42834"], "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:38854719", "parent_hash": "sha256:217c28a383a18724881b9f390c11256fdb74a0293be0191ba0e60aee4724472d", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE42834 licence not read", "asset:data:geo:GSE42834 not downloaded", "asset:data:geo:GSE43458 licence not read", "asset:data:geo:GSE43458 not downloaded", "asset:data:geo:GSE83456 licence not read", "asset:data:geo:GSE83456 not downloaded", "asset:data:geo:PRJNA1080061 licence not read", "asset:data:geo:PRJNA1080061 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["pathway enrichment"], "order_basis": "analysis_only", "id": "assay:1"}]}