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pmid:37426635
Identifying hub genes and common biological pathways between COVID-19 and benign prostatic hyperplasia by machine learning algorithms.
Hang Zhou · Mingming Xu · Ping Hu · Yuezheng Li · Congzhe Ren · Muwei Li · Yang Pan · Shangren Wang · Xiaoqiang Liu
Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1172724
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Experiment
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Data
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Analysis
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Complete file
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The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms.\nMethods: We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the \"Limma\" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses.\nResults: We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the P value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH.\nConclusion: Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.", "claims": [{"id": "claim-method", "statement": "With adj. P < 0.05 and |log2FC| > 0.263 for GSE157103 and adj. P < 0.05 and |log2FC| > 1 for GSE7307, the DEGs were found using the “Limma” R package (29).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37426635", "locator": "sections[4] \"Identification of common DEGs\" paragraph 2", "quote": "With adj. P < 0.05 and |log2FC| > 0.263 for GSE157103 and adj. P < 0.05 and |log2FC| > 1 for GSE7307, the DEGs were found using the “Limma” R package (29)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37426635", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37426635", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets.", "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:37426635"], "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:GSE132714"], "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:GSE132714"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37426635", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1172724", "sha256": "sha256:d42f99a05424267b685d619e327a2e223f874502561307ca3b5d26eaedaae44c", "bytes": 56449, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1172724", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10328422", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE132714", "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=GSE132714", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE132714", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . 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null, "platform": "570", "taxon": "Homo sapiens", "title": "Human body index - transcriptional profiling", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE132714 not downloaded", "asset:data:geo:GSE132714 licence not read", "asset:data:geo:GSE157103 not downloaded", "asset:data:geo:GSE157103 licence not read", "asset:data:geo:GSE166253 not downloaded", "asset:data:geo:GSE166253 licence not read", "asset:data:geo:GSE7307 not downloaded", "asset:data:geo:GSE7307 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": 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P < 0.05 and |log2FC| > 0.263 for GSE157103 and adj. P < 0.05 and |log2FC| > 1 for GSE7307, the DEGs were found using the “Limma” R package (29)."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "Protein-Protein Interaction"}}], "targets": [], "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": ["GSE157103", "GSE166253", "GSE7307", "GSE132714"], "resolved_accessions": ["GSE157103", "GSE166253", "GSE7307", "GSE132714"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE157103, GSE166253, GSE7307, GSE132714 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:37426635", "data:geo:GSE132714"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE132714"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:46:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17029, "completion_tokens": 1522, "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:37426635", "type": "paper", "label": "pmid:37426635"}, {"id": "source:pmid:37426635", "type": "manuscript", "label": "PMID 37426635 full text"}, {"id": "data:geo:GSE132714", "type": "dataset", "label": "GEO GSE132714"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37426635", "type": "paper", "label": "pmid:37426635"}, {"id": "source:pmid:37426635", "type": "manuscript", "label": "PMID 37426635 full text"}, {"id": "data:geo:GSE132714", "type": "dataset", "label": "GEO GSE132714"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37426635", "type": "extraction", "used": ["source:pmid:37426635"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE132714", "type": "accession_resolution", "used": ["data:geo:GSE132714"], "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:37426635", "parent_hash": "sha256:b0436ecced78d27ff8d26d7b2757170ee13f1985478693019933f75d9f76a4d6", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE132714 licence not read", "asset:data:geo:GSE132714 not downloaded", "asset:data:geo:GSE157103 licence not read", "asset:data:geo:GSE157103 not downloaded", "asset:data:geo:GSE166253 licence not read", "asset:data:geo:GSE166253 not downloaded", "asset:data:geo:GSE7307 licence not read", "asset:data:geo:GSE7307 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": ["With adj. P < 0.05 and |log2FC| > 0.263 for GSE157103 and adj. P < 0.05 and |log2FC| > 1 for GSE7307, the DEGs were found using the “Limma” R package (29)."], "order_basis": "analysis_only", "id": "assay:1"}]}