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pmid:37026011
Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis.
Xianxian Jia · Hua Zhu · Qinglian Jiang · Jia Gu · Shihan Yu · Xuyang Chi · Rui Wang · Yu Shan · Hong Jiang · Xiaoxue Ma
Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1087293
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Experiment
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Analysis
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Complete file
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This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAVN.\nMethods: GSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAVN.\nResult: A total of 4200 DEGs were screened in IgAVN patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, STAT1, TLR4, PTEN, UBB, HSPA8, ATP5B, UBA52, and CDC42 were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAVN, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAVN.\nConclusion: We screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAVN. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAVN.", "claims": [{"id": "claim-method", "statement": "Subsequently, the differentially expressed genes between IgAVN patients and HD were calculated using the edgeR package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37026011", "locator": "sections[3] \"Data collection and identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "Subsequently, the differentially expressed genes between IgAVN patients and HD were calculated using the edgeR package in R."}], "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:37026011", "locator": "sections[19] \"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": "A total of 4,200 DEGs were identified in IgAVN samples compared with healthy-donor samples.", "kind": "quantitative", "target": {"value": 2.0, "unit": "fold change", "tolerance": null, "source": "A total of 4,200 DEGs were screened (|Log2fold change| > 2, adjusted p < 0.05) based on the analysis in IgAVN samples compared to HD samples, which contained 2,102 genes with upregulated and 2,098 with downregulated expression."}, "evidence": [{"asset": "source:pmid:37026011", "locator": "sections[13] \"Identification of differential expressed mRNA between IgAVN patients and HD\" paragraph 4", "quote": "A total of 4,200 DEGs were screened (|Log2fold change| > 2, adjusted p < 0.05) based on the analysis in IgAVN samples compared to HD samples, which contained 2,102 genes with upregulated and 2,098 with downregulated expression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 4,200 DEGs were identified in IgAVN samples compared with healthy-donor samples.", "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:37026011"], "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:GSE102114"], "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:GSE102114"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37026011", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1087293", "sha256": "sha256:90e56671fce5cc1d5b145fd77a092243d1ceae7a933cab0b099b1d622a190cc2", "bytes": 32518, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1087293", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10070996", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE102114", "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=GSE102114", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE102114", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material , Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material , Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2724040", "GSM2724041", "GSM2724042", "GSM2724043", "GSM2724044", "GSM2724045", "GSM2724046", "GSM2724047", "GSM2724048", "GSM2724049"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Differential expression of long non‑coding RNA and mRNA in children with Henoch‑Schönlein purpura nephritis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE102114 not downloaded", "asset:data:geo:GSE102114 licence not read"]}, "analysis": {"state": "partial", "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": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Subsequently, the differentially expressed genes between IgAVN patients and HD were calculated using the edgeR package in R."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "PCA"}}, {"id": "method-3", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-4", "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": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 2.0, "unit": "fold change", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. 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