Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34124269", "kind": "science-record", "revision": 7, "content_hash": "sha256:0379eeeab9eb91a17a5f0077f5684061b817b26e266792477bd9d3623a9f6aac", "created_at": "2026-11-01T15:41:38Z", "updated_at": "2026-11-01T22:03:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.", "doi": "10.1155/2021/5546199", "pmid": "34124269", "authors": ["Bojun Xu", "Lei Wang", "Huakui Zhan", "Liangbin Zhao", "Yuehan Wang", "Meng Shen", "Keyang Xu", "Li Li", "Xu Luo", "Shasha Zhou", "Anqi Tang", "Gang Liu", "Lu Song", "Yan Li"], "journal": "Journal of diabetes research", "year": 2021, "abstract": "OBJECTIVES: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients.\nMETHODS: GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN.\nRESULTS: There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN.\nCONCLUSIONS: We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.", "claims": [{"id": "claim-method", "statement": "Pearson's correlation analysis between hub genes and glomerular filtration rate (GFR) in patients with DN was conducted via applying Nephroseq v5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34124269", "locator": "sections[7] \"2.5. Statistical Analysis\" paragraph 2", "quote": "Pearson's correlation analysis between hub genes and glomerular filtration rate (GFR) in patients with DN was conducted via applying Nephroseq v5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are included within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34124269", "locator": "sections[16] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are included within the article."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34124269"], "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:GSE104948"], "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:GSE104948"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34124269", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/5546199", "sha256": 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"identifier": "section[10]/table-wrap[1]#tab1", "version": null, "note": "The most significant clusters of common DEGs.", "structure": {"pmcid": "PMC8169258", "section_index": 10, "section_title": "3.2. PPI Network Analysis and Hub Gene Selection", "row_count": 4, "column_count": 6}, "table": {"label": "Table 1", "caption": "The most significant clusters of common DEGs.", "rows": [["Cluster", "Network", "Nodes", "Edges", "Score", "Cluster genes"], ["1", "", "21", "203", "20.3", "EVI2A, RNASE6, LAPTM5, LYZ, CD53, CLEC10A, TYROBP, DOCK2, ALOX5, IL10RA, C1QA, MS4A6A, CD52, C1QB, ITGB2, MS4A4A, CD48, CD163, VSIG4, CYBB, IRF8"], ["2", "", "13", "62", "10.3", "TGFBI, VCAN, THBS2, CFB, CLU, COL1A2, IGFBP3, COL6A3, LUM, KRT19, TNC, PROM1, TAGLN"], ["3", "", "7", "21", "7", "CD44, ALB, FN1, CCL5, SERPINF1, IGF1, C3"]], "row_count": 4, "column_count": 6, "numeric_cells": 15, "header_rows": 1, "locator": "section[10]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:34124269:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ac02d06790fa17a7b005235747d191309eb4edc497191b6161da31297cd2e6cb", "bytes": 2894, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[2]#tab2", "version": null, "note": "Hub genes of diabetic nephropathy.", "structure": {"pmcid": "PMC8169258", "section_index": 10, "section_title": "3.2. PPI Network Analysis and Hub Gene Selection", "row_count": 35, "column_count": 8}, "table": {"label": "Table 2", "caption": "Hub genes of diabetic nephropathy.", "rows": [["Groups", "Gene symbol", "GSE30528", "GSE104948", "GSE47183"], ["LogFC", "P value", "LogFC", "P value", "LogFC", "P value"], ["Up", "FN1", "1.540307", "1.86E − 06", "1.688679", "6.53E − 14", "1.411328", "0.000115"], ["CD44", "1.410913", "0.00288", "1.154713", "1.03E − 09", "1.118944", "0.004117"], ["ITGB2", "1.288601", "0.000137", "1.624558", "1.71E − 09", "1.176759", "0.015233"], ["CCL5", "1.720493", "0.000615", "1.281747", "1.58E − 08", "1.010635", "0.002817"], ["CD163", "1.973348", "2.66E − 06", "1.260515", "4.52E − 05", "2.25682", "0.006126"], ["C1QA", "1.922276", "3.04E − 08", "2.469202", "7.39E − 08", "2.643819", "0.002315"], ["C1QB", "2.204686", "4.22E − 07", "2.123409", "8.65E − 08", "2.331991", "0.003483"], ["CYBB", "1.082376", "2.88E − 05", "1.559454", "6.84E − 10", "1.081369", "0.01398"], ["TYROBP", "1.3831", "0.000242", "2.191158", "1.95E − 08", "1.720981", "0.000578"], ["LYZ", "1.529532", "0.00258", "2.79008", "2.08E − 08", "1.693295", "0.000448"], ["CD48", "1.736706", "0.000071", "2.1464", "7.11E − 11", "1.271107", "0.002955"], ["IL10RA", "1.468163", "0.000276", "1.928371", "3.65E − 09", "1.340032", "0.004027"], ["CLEC10A", "1.005234", "6.1E − 06", "1.197336", "6.34E − 07", "1.050224", "0.032825"], ["COL1A2", "2.590987", "9.18E − 06", "2.656871", "2.14E − 07", "2.275034", "0.005026"], ["CLU", "1.472253", "0.000508", "1.734574", "1.59E − 06", "1.912975", "0.002851"], ["C3", "2.679961", "0.000157", "2.281075", "3.84E − 06", "2.430408", "0.017567"], ["IRF8", "1.583247", "0.000131", "1.488973", "1.09E − 06", "1.493004", "0.005593"], ["CD52", "2.232654", "9.78E − 05", "2.140349", "6.98E − 13", "1.169746", "0.007569"], ["TGFBI", "1.32786", "0.000642", "2.396142", "3.41E − 13", "2.168562", "3.43E − 05"], ["ALOX5", "1.673735", "0.00568", "1.450238", "7.51E − 09", "1.277775", "0.001606"], ["CD53", "1.672055", "5.65E − 05", "1.74099", "5.92E − 08", "1.230233", "0.012145"], ["VSIG4", "1.576657", "5.22E − 06", "1.696336", "1.31E − 07", "1.919467", "0.003"], ["CFB", "1.720388", "6.19E − 05", "1.382782", "5.74E − 05", "1.365459", "0.021665"], ["IGFBP3", "1.033501", "9.66E − 05", "1.23278", "0.000966", "2.409502", "0.002813"], ["LAPTM5", "1.062031", "0.00158", "1.554621", "9.52E − 08", "1.238422", "0.001673"], ["MS4A6A", "1.869037", "6.81E − 06", "2.054775", "9.74E − 09", "1.959976", "0.00497"], ["LUM", "2.374619", "4.49E − 05", "1.843351", "0.00363", "3.496266", "0.004413"], ["VCAN", "1.273776", "0.00177", "1.33971", "4.88E − 05", "1.440879", "0.034958"], ["MS4A4A", "1.446755", "2.65E − 05", "2.039072", "1.15E − 08", "1.994681", "0.00792"], ["DOCK2", "1.009537", "0.0028", "1.457016", "1.34E − 09", "1.181051", "0.003642"], [""], ["Down", "ALB", "-1.78623", "0.00896", "-2.38803", "0.000092", "-2.63068", "0.007517"], ["IGF1", "-2.57456", "7.11E − 05", "-1.6702", 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