Identification of miRNA-mRNA network and immune-related gene signatures in IgA nephropathy by integrated bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34823491", "kind": "science-record", "revision": 4, "content_hash": "sha256:90dfffb7b4255b919230fe6f1974bbe5e17173266effc716fb82bdaec271ef1c", "created_at": "2026-11-01T17:36:31Z", "updated_at": "2026-11-01T22:05:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of miRNA-mRNA network and immune-related gene signatures in IgA nephropathy by integrated bioinformatics analysis.", "doi": "10.1186/s12882-021-02606-5", "pmid": "34823491", "authors": ["Shi-Yao Wei", "Shuang Guo", "Bei Feng", "Shang-Wei Ning", "Xuan-Yi Du"], "journal": "BMC nephrology", "year": 2021, "abstract": "BACKGROUND: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, and its diagnosis depends mainly on renal biopsy. However, there is no specific treatment for IgAN. Moreover, its causes and underlying molecular events require further exploration.\nMETHODS: The expression profiles of GSE64306 and GSE93798 were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differential expression of miRNAs and genes, respectively. The StarBase and TransmiR databases were employed to predict target genes and transcription factors of the differentially expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to predict biological functions. A comprehensive analysis of the miRNA-mRNA regulatory network was constructed, and protein-protein interaction (PPI) networks and hub genes were identified. CIBERSORT was used to examine the immune cells in IgAN, and correlation analyses were performed between the hub genes and infiltrating immune cells.\nRESULTS: Four downregulated miRNAs and 16 upregulated miRNAs were identified. Forty-five and twelve target genes were identified for the upregulated and downregulated DE-miRNAs, respectively. CDKN1A, CDC23, EGR1, HIF1A, and TRIM28 were the hub genes with the highest degrees of connectivity. CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN. Additionally, HIF1A, CDC23, TRIM28, and CDKN1A in IgAN patients were associated with immune cell infiltration.\nCONCLUSIONS: A potential miRNA-mRNA regulatory network contributing to IgAN onset and progression was successfully established. The results of the present study may facilitate the diagnosis and treatment of IgAN by targeting established miRNA-mRNA interaction networks. Infiltrating immune cells may play significant roles in IgAN pathogenesis. Future studies on these immune cells may help guide immunotherapy for IgAN patients.", "claims": [{"id": "claim-method", "statement": "The Wilcoxon rank sum test was used to calculate the differences in the levels of immune cell infiltration between IgAN and normal samples (P < 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34823491", "locator": "sections[8] \"Evaluation of infiltrated immune cells in IgAN\" paragraph 2", "quote": "The Wilcoxon rank sum test was used to calculate the differences in the levels of immune cell infiltration between IgAN and normal samples (P < 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34823491", "locator": "sections[30] \"notes\" paragraph 1", "quote": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34823491", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN.", "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:34823491"], "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:GSE37460"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE37460"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34823491", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12882-021-02606-5", "sha256": "sha256:43eb9d74833d96df40853bcbe4ad77ee5c815595ce124b2248ba007e06bbf40f", "bytes": 38623, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12882-021-02606-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8620631", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE37460", "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=GSE37460", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE37460", "version": null, "note": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1046922", "GSM1046923", "GSM1046924", "GSM1046925", "GSM1046926", "GSM920350", "GSM920351", "GSM920352", "GSM920353", "GSM920368", "GSM920369", "GSM920370", "GSM920371", "GSM920372", "GSM920373", "GSM920374", "GSM920375", "GSM920376", "GSM920377", "GSM920378", "GSM920379", "GSM920380", "GSM920381", "GSM920382", "GSM920383", "GSM920384", "GSM920385", "GSM920386", "GSM920387", "GSM920388", "GSM920389", "GSM920390", "GSM920391", "GSM920392", "GSM920393", "GSM920394", "GSM920395", "GSM920396", "GSM920397", "GSM920398", "GSM920399", "GSM920400", "GSM920401", "GSM920402", "GSM920403", "GSM920404", "GSM920405", "GSM920406", "GSM920407", "GSM920408", "GSM920409", "GSM920410", "GSM920411", "GSM920412", "GSM920413", "GSM920414", "GSM920415", "GSM920416", "GSM920417", "GSM920418", "GSM920419", "GSM920420", "GSM920421", "GSM920422", "GSM920423", "GSM920424", "GSM920425", "GSM920426", "GSM920427"], "sample_count": 69, "group_sizes": null, "group_sizes_basis": null, "platform": "14663;11670", "taxon": "Homo sapiens", "title": "Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis [Glomeruli]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE64306", "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=GSE64306", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE64306", "version": null, "note": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1568359", "GSM1568360", "GSM1568361", "GSM1568362", "GSM1568363", "GSM1568364", "GSM1568365", "GSM1568366", "GSM1568367", "GSM1568368", "GSM1568369", "GSM1568370", "GSM1568371", "GSM1568372", "GSM1568373", "GSM1568374", "GSM1568375", "GSM1568376", "GSM1568377", "GSM1568378", "GSM1568379", "GSM1568380", "GSM1568381", "GSM1568382", "GSM1568383", "GSM1568384", "GSM1568385", "GSM1568386", "GSM1568387", "GSM1568388", "GSM1568389", "GSM1568390"], "sample_count": 32, "group_sizes": null, "group_sizes_basis": null, "platform": "19117", "taxon": "synthetic construct; Homo sapiens", "title": "MicroRNA profiling by array of human urinary sediments from IgAN patients", "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:GSE93798", "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=GSE93798", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE93798", "version": null, "note": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2462533", "GSM2462534", "GSM2462535", "GSM2462536", "GSM2462537", "GSM2462538", "GSM2462539", "GSM2462540", "GSM2462541", "GSM2462542", "GSM2462543", "GSM2462544", "GSM2462545", "GSM2462546", "GSM2462547", "GSM2462548", "GSM2462549", "GSM2462550", "GSM2462551", "GSM2462552", "GSM2462553", "GSM2462554", "GSM2462555", "GSM2462556", "GSM2462557", "GSM2462558", "GSM2462559", "GSM2462560", "GSM2462561", "GSM2462562", "GSM2462563", "GSM2462564", "GSM2462565", "GSM2462566", "GSM2462567", "GSM2462568", "GSM2462569", "GSM2462570", "GSM2462571", "GSM2462572", "GSM2462573", "GSM2462574"], "sample_count": 42, "group_sizes": null, "group_sizes_basis": null, "platform": "22945", "taxon": "Homo sapiens", "title": "Transcriptomic and proteomic profiling reveal insights of mesangial cell function in patients with IgA Nephropathy", "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:GSE37460 not downloaded", "asset:data:geo:GSE37460 licence not read", "asset:data:geo:GSE64306 not downloaded", "asset:data:geo:GSE64306 licence not read", "asset:data:geo:GSE93798 not downloaded", "asset:data:geo:GSE93798 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Wilcoxon rank sum test was used to calculate the differences in the levels of immune cell infiltration between IgAN and normal samples (P < 0.05)."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-3", "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": ["method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": ["GSE64306", "GSE93798", "GSE37460"], "resolved_accessions": ["GSE64306", "GSE93798", "GSE37460"], "statements": ["The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. The datasets generated and analyzed during the current study are available in the GEO repository (GSE64306, GSE93798, and GSE37460). The gene expression profile was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE64306, GSE93798, GSE37460 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:34823491", "data:geo:GSE37460"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE37460"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:08:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10594, "completion_tokens": 1883, "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:34823491", "type": "paper", "label": "pmid:34823491"}, {"id": "source:pmid:34823491", "type": "manuscript", "label": "PMID 34823491 full text"}, {"id": "data:geo:GSE37460", "type": "dataset", "label": "GEO GSE37460"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34823491", "type": "paper", "label": "pmid:34823491"}, {"id": "source:pmid:34823491", "type": "manuscript", "label": "PMID 34823491 full text"}, {"id": "data:geo:GSE37460", "type": "dataset", "label": "GEO GSE37460"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34823491", "type": "extraction", "used": ["source:pmid:34823491"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE37460", "type": "accession_resolution", "used": ["data:geo:GSE37460"], "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:34823491", "parent_hash": "sha256:7f69135a2d059d8b2be6a580d5b16c5ad95926150b74e95e2d662a9ffe3bae5d", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE37460 licence not read", "asset:data:geo:GSE37460 not downloaded", "asset:data:geo:GSE64306 licence not read", "asset:data:geo:GSE64306 not downloaded", "asset:data:geo:GSE93798 licence not read", "asset:data:geo:GSE93798 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "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": ["cessing and differential expression analysis Microarray data were processed and analyzed in R. By co"], "order_basis": "paper_text_order:2201", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Wilcoxon rank sum test was used to calculate the differences in the levels of immune cell infiltration between IgAN and normal samples (P < 0.05)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}