Network-Based Data Analysis Reveals Ion Channel-Related Gene Features in COVID-19: A Bioinformatic Approach.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36104591", "kind": "science-record", "revision": 5, "content_hash": "sha256:cdc8dbf5577f65bc0c7bd31eb9eacb484617c719726daaabf7119498a3f6d03e", "created_at": "2026-11-01T18:15:20Z", "updated_at": "2026-11-01T22:50:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Network-Based Data Analysis Reveals Ion Channel-Related Gene Features in COVID-19: A Bioinformatic Approach.", "doi": "10.1007/s10528-022-10280-x", "pmid": "36104591", "authors": ["Hao Zhang", "Ting Feng"], "journal": "Biochemical genetics", "year": 2023, "abstract": "Coronavirus disease 2019 (COVID-19) seriously threatens human health and has been disseminated worldwide. Although there are several treatments for COVID-19, its control is currently suboptimal. Therefore, the development of novel strategies to treat COVID-19 is necessary. Ion channels are located on the membranes of all excitable cells and many intracellular organelles and are key components involved in various biological processes. They are a target of interest when searching for drug targets. This study aimed to reveal the relevant molecular features of ion channel genes in COVID-19 based on bioinformatic analyses. The RNA-sequencing data of patients with COVID-19 and healthy subjects (GSE152418 and GSE171110 datasets) were obtained from the Gene Expression Omnibus (GEO) database. Ion channel genes were selected from the Hugo Gene Nomenclature Committee (HGNC) database. The RStudio software was used to process the data based on the corresponding R language package to identify ion channel-associated differentially expressed genes (DEGs). Based on the DEGs, Gene Ontology (GO) functional and pathway enrichment analyses were performed using the Enrichr web tool. The STRING database was used to generate a protein-protein interaction (PPI) network, and the Cytoscape software was used to screen for hub genes in the PPI network based on the cytoHubba plug-in. Transcription factors (TF)-DEG, DEG-microRNA (miRNA) and DEG-disease association networks were constructed using the NetworkAnalyst web tool. Finally, the screened hub genes as drug targets were subjected to enrichment analysis based on the DSigDB using the Enrichr web tool to identify potential therapeutic agents for COVID-19. A total of 29 ion channel-associated DEGs were identified. GO functional analysis showed that the DEGs were integral components of the plasma membrane and were mainly involved in inorganic cation transmembrane transport and ion channel activity functions. Pathway analysis showed that the DEGs were mainly involved in nicotine addiction, calcium regulation in the cardiac cell and neuronal system pathways. The top 10 hub genes screened based on the PPI network included KCNA2, KCNJ4, CACNA1A, CACNA1E, NALCN, KCNA5, CACNA2D1, TRPC1, TRPM3 and KCNN3. The TF-DEG and DEG-miRNA networks revealed significant TFs (FOXC1, GATA2, HINFP, USF2, JUN and NFKB1) and miRNAs (hsa-mir-146a-5p, hsa-mir-27a-3p, hsa-mir-335-5p, hsa-let-7b-5p and hsa-mir-129-2-3p). Gene-disease association network analysis revealed that the DEGs were closely associated with intellectual disability and cerebellar ataxia. Drug-target enrichment analysis showed that the relevant drugs targeting the hub genes CACNA2D1, CACNA1A, CACNA1E, KCNA2 and KCNA5 were gabapentin, gabapentin enacarbil, pregabalin, guanidine hydrochloride and 4-aminopyridine. The results of this study provide a valuable basis for exploring the mechanisms of ion channel genes in COVID-19 and clues for developing therapeutic strategies for COVID-19.", "claims": [{"id": "claim-method", "statement": "The RNA-Seq data of patients with COVID-19 (GSE152418 and GSE171110) were processed using RStudio based on the edgeR R package (version 3.36.0). The cut-off criteria of false discovery rate (FDR) < 0.05 and absolute value of log2-fold change (|logFC|) ≥ 1.0 were used to screen for significant DEGs in the abovementioned datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36104591", "locator": "sections[4] \"Screening of Differential Genes\" paragraph 2", "quote": "The RNA-Seq data of patients with COVID-19 (GSE152418 and GSE171110) were processed using RStudio based on the edgeR R package (version 3.36.0). The cut-off criteria of false discovery rate (FDR) < 0.05 and absolute value of log2-fold change (|logFC|) ≥ 1.0 were used to screen for significant DEGs in the abovementioned datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36104591", "locator": "sections[23] \"notes\" paragraph 1", "quote": "The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 29 ion channel-associated differentially expressed genes were identified in the COVID-19 RNA-sequencing datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36104591", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 29 ion channel-associated DEGs were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 29 ion channel-associated differentially expressed genes were identified in the COVID-19 RNA-sequencing datasets.", "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:36104591"], "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:GSE152418"], "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": {"fdr_threshold": "ession analysis using a false discovery rate cutoff of < 0"}, "inputs": ["data:geo:GSE152418"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36104591", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10528-022-10280-x", "sha256": "sha256:15371ed80f02ba45cdb6da211d108484b243a489c2c1929a7ffbb9aca83ab0e5", "bytes": 54180, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10528-022-10280-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9473477", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE152418", "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=GSE152418", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE152418", "version": null, "note": "The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4614985", "GSM4614986", "GSM4614987", "GSM4614988", "GSM4614989", "GSM4614990", "GSM4614991", "GSM4614992", "GSM4614993", "GSM4614994", "GSM4614995", "GSM4614996", "GSM4614997", "GSM4614998", "GSM4614999", "GSM4615000", "GSM4615001", "GSM4615003", "GSM4615006", "GSM4615008", "GSM4615011", "GSM4615014", "GSM4615016", "GSM4615019", "GSM4615022", "GSM4615025", "GSM4615027", "GSM4615030", "GSM4615032", "GSM4615033", "GSM4615034", "GSM4615035", "GSM4615036", "GSM4615037"], "sample_count": 34, "group_sizes": null, "group_sizes_basis": null, "platform": "24676", "taxon": "Homo sapiens", "title": "Systems biological assessment of immunity to severe and mild COVID-19 infections", "resolution_checked_at": "2026-11-01T18:06:43Z", "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": "The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article.", "access_statement_kind": "data_availability_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:GSE152418 not downloaded", "asset:data:geo:GSE152418 licence not read", "asset:data:geo:GSE171110 not downloaded", "asset:data:geo:GSE171110 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fdr_threshold": "ession analysis using a false discovery rate cutoff of < 0"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The RNA-Seq data of patients with COVID-19 (GSE152418 and GSE171110) were processed using RStudio based on the edgeR R package (version 3.36.0). The cut-off criteria of false discovery rate (FDR) < 0.05 and absolute value of log2-fold change (|logFC|) ≥ 1.0 were used to screen for significant DEGs in the abovementioned datasets."}}, {"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"}}, {"id": "method-3", "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": [], "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: edger."}, "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": ["GSE152418", "GSE171110"], "resolved_accessions": ["GSE152418", "GSE171110"], "statements": ["The datasets analysed in the study are available at the public database NCBI GEO (https:// www.ncbi.nlm.nih.gov/geo/). All data generated or analysed during this study are included in this published article."], "basis": "The paper names GSE152418, 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:36104591", "data:geo:GSE152418"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE152418"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:05:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15794, "completion_tokens": 1315, "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:36104591", "type": "paper", "label": "pmid:36104591"}, {"id": "source:pmid:36104591", "type": "manuscript", "label": "PMID 36104591 full text"}, {"id": "data:geo:GSE152418", "type": "dataset", "label": "GEO GSE152418"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36104591", "type": "paper", "label": "pmid:36104591"}, {"id": "source:pmid:36104591", "type": "manuscript", "label": "PMID 36104591 full text"}, {"id": "data:geo:GSE152418", "type": "dataset", "label": "GEO GSE152418"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36104591", "type": "extraction", "used": ["source:pmid:36104591"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE152418", "type": "accession_resolution", "used": ["data:geo:GSE152418"], "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:36104591", "parent_hash": "sha256:1c15a7cd3c7868cb659144acd0aff6e7a67b26f13756f9159d1b16427fb1773f", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE152418 licence not read", "asset:data:geo:GSE152418 not downloaded", "asset:data:geo:GSE171110 licence not read", "asset:data:geo:GSE171110 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["OVID-19 based on bioinformatic analyses. The RNA-sequencing data of patients with COVID-19 and healthy s"], "order_basis": "paper_text_order:694", "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": ["The RNA-Seq data of patients with COVID-19 (GSE152418 and GSE171110) were processed using RStudio based on the edgeR R package (version 3.36.0). The cut-off criteria of false discovery rate (FDR) < 0.05 and absolute value of log2-fold change (|logFC|) ≥ 1.0 were used to screen for significant DEGs in the abovementioned datasets."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}