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pmid:32426333
Dysregulation of Signaling Pathways Due to Differentially Expressed Genes From the B-Cell Transcriptomes of Systemic Lupus Erythematosus Patients - A Bioinformatics Approach.
S Udhaya Kumar · D Thirumal Kumar · R Siva · C George Priya Doss · Salma Younes · Nadin Younes · Mariem Sidenna · Hatem Zayed
Frontiers in bioengineering and biotechnology · 2020 doi:10.3389/fbioe.2020.00276
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Complete file
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Via emerging technologies, researchers have identified genetic variants, expression profiling of genes, animal models, and epigenetic findings that have paved the way for a better understanding of the molecular and genetic mechanisms of SLE. Our current study aimed to illustrate the essential genes and molecular pathways that are potentially involved in the pathogenesis of SLE. This study incorporates the gene expression profiling data of the microarray dataset GSE30153 from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between the B-cell transcriptomes of SLE patients and healthy controls were screened using the GEO2R web tool. The identified DEGs were subjected to STRING analysis and Cytoscape to explore the protein-protein interaction (PPI) networks between them. The MCODE (Molecular Complex Detection) plugin of Cytoscape was used to screen the cluster subnetworks that are highly interlinked between the DEGs. Subsequently, the clustered DEGs were subjected to functional annotation with ClueGO/CluePedia to identify the significant pathways that were enriched. For integrative analysis, we used GeneGo MetacoreTM, a Cortellis Solution software, to exhibit the Gene Ontology (GO) and enriched pathways between the datasets. Our study identified 4 upregulated and 13 downregulated genes. Analysis of GO and functional enrichment using ClueGO revealed the pathways that were statistically significant, including pathways involving T-cell costimulation, lymphocyte costimulation, negative regulation of vascular permeability, and B-cell receptor signaling. The DEGs were mainly enriched in metabolic networks such as the phosphatidylinositol-3,4,5-triphosphate pathway and the carnitine pathway. Additionally, potentially enriched pathways, such as the signaling pathways induced by oxidative stress and reactive oxygen species (ROS), chemotaxis and lysophosphatidic acid signaling induced via G protein-coupled receptors (GPCRs), and the androgen receptor activation pathway, were identified from the DEGs that were mainly associated with the immune system. Four genes (EGR1, CD38, CAV1, and AKT1) were identified to be strongly associated with SLE. Our integrative analysis using a multitude of bioinformatics tools might promote an understanding of the dysregulated pathways that are associated with SLE development and progression. The four DEGs in SLE patients might shed light on the pathogenesis of SLE and might serve as potential biomarkers in early diagnosis and as therapeutic targets for SLE.", "claims": [{"id": "claim-method", "statement": "We performed a Benjamini–Hochberg test (to determine the false discovery rate) and T-tests to compute the false discovery rate (FDR) and p-values to identify the DEGs between SLE patients and healthy control human sorted B-cells", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32426333", "locator": "sections[4] \"Preprocessing of Data and DEG Identification\" paragraph 2", "quote": "We performed a Benjamini–Hochberg test (to determine the false discovery rate) and T-tests to compute the false discovery rate (FDR) and p-values to identify the DEGs between SLE patients and healthy control human sorted B-cells"}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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"media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cea73c541499c2c3a0299bf3dd01cf71cf64c2df9cd0f482d31df78dd0d55540", "bytes": 4369, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#T4", "version": null, "note": "The interaction reports of key genes from pathway maps by Clarivate Analytics.", "structure": {"pmcid": "PMC7203449", "section_index": 12, "section_title": "Pathway Map Interaction Results From Clarivate", "row_count": 5, "column_count": 11}, "table": {"label": "TABLE 4", "caption": "The interaction reports of key genes from pathway maps by Clarivate Analytics.", "rows": [["Network object “from”", "Object type", "Network object “to”", "Object type", "Effect", "Mechanism", "Link info", "Input IDs", "Signal", "P-value", "PMID"], ["EGR1", "Transcription factor", "IGF-2, APEX, SRD5A1, CD44, EGFR", "Receptor ligand, generic enzyme, generic enzyme, generic receptor, 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required to induce proliferation in mouse B-lymphocytes, Fluorescence resource energy transfer and coimmunoprecipitation showed that c-Cbl and CD38 bind each other.", "CD38", "1", "0.0031747", "15613544; 17327405; 20570673; 22564057; 8695807; 18974118; 19635790"], ["CAV1", "Generic binding protein", "ErbB2, MDR1, HTR2A, Androgen receptor", "Receptor with enzyme activity, transporter, GPCR, transcription factor", "Unspecified, Inhibition, activation", "Binding", "HER2 physically interacts with caveolin-1, Caveolin-1 interacts with p-gp, Down-regulation of caveolin-1 by siRNA reduced the interaction between p-gp and caveolin-1, followed by a decrease in [3H]-Taxol and [3H]-Vinblastine accumulation in RBE4 cells, Caveolin-1 physically interacts with HTR2A and increases its activity, Highly conserved 9 amino acid motif in the ligand binding domains (E domains) was identified in human/mouse ER alpha and ER beta, progesterone receptors A and B, and the androgen receptor. The localization sequence mediated palmitoylation of each SR, which facilitated caveolin-1 association, subsequent membrane localization, and steroid signaling.", "CAV1", "1", "0.0048324", "9374534; 9685399; 11697880; 22389470; 14622130; 15239129; 15498565; 17326770; 18485890; 19099191; 22389470; 25788263; 15190056; 8703009; 11278309; 17535799; 17940184; 18786521; 19931639; 22771325; 24375805"], ["AKT1, AKT (PKB)", "Protein kinase", "FKHR, mTOR, Bcl-10, FOXO3A, HNF3-beta, GSK3 beta", "Transcription factor, protein kinase, generic binding protein", "Inhibition, activation", "Phosphorylation", "AKT1 phosphorylates FKHR1 and decreases its activity, Increased AKT phosphorylation regulates different metabolic pathways in liver, including increases in protein synthesis through activation of mTOR/p70 (S6kinase), AKT1 phosphorylates Bcl-10 and increases its activity, AKT1 phosphorylates FOXO3A and decreases its activity, AKT1 phosphorylates HNF3-beta and decreases its activity, AKT (PKB) inhibits GSK3 alpha by phosphorylation at Ser-9.", "AKT1", "1", "0.0010146", "10102273; 10358014; 10358075; 10377430; 11030146; 12393870; 16076959; 16099987; 16230533; 16603397; 17186497; 18388859; 18391970; 18420577; 18687691; 18786403; 19703413; 20940043; 21106439; 21157483; 21238503; 21407213; 21440577; 21708191; 21779512; 26053093; 27966458; 30413788; 10567225; 10910062; 11357143; 11438723; 12767043; 14970221; 15208671; 15549092; 16818631; 17660512; 18505677; 18566586; 18566587; 18678273; 21097843; 21177249; 21302298; 21343617; 22084251; 22595285; 23686889; 23872070; 26958938; 29221131; 16280327; 10102273; 12130673; 12767043; 17570479; 17577629; 17957242; 17960591; 18391970; 18687691; 19703413; 20223831; 20399660; 21106439; 21157483; 21440577; 21621563; 21708191; 21775285; 21779512; 24518891; 27966458; 14500912; 11584303; 11701324; 12124352; 12750378; 12808085; 14966899; 14985354; 15016802; 15297258"]], "row_count": 5, "column_count": 11, "numeric_cells": 21, "header_rows": 1, "locator": "section[12]/table-wrap[1]#T4"}}], "gaps": ["asset:data:geo:GSE30153 not downloaded", "asset:data:geo:GSE30153 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "Benjamini–Hochberg test and T-tests", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We performed a Benjamini–Hochberg test (to determine the false discovery rate) and T-tests to compute the false discovery rate (FDR) and p-values to identify the DEGs between SLE patients and healthy control human sorted B-cells"}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE30153"], "resolved_accessions": ["GSE30153"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30153."], "basis": "The paper names GSE30153 in NCBI GEO database (Gene Expression Omnibus database) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:32426333", "data:geo:GSE30153", "asset:table:pmid:32426333:1", "asset:table:pmid:32426333:2", "asset:table:pmid:32426333:3", "asset:table:pmid:32426333:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30153"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:20:00Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 29453, "completion_tokens": 1378, "cached_tokens": 784}}, "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:32426333", "type": "paper", "label": "pmid:32426333"}, {"id": "source:pmid:32426333", "type": "manuscript", "label": "PMID 32426333 full text"}, {"id": "data:geo:GSE30153", "type": "dataset", "label": "GEO GSE30153"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32426333", "type": "paper", "label": "pmid:32426333"}, {"id": "source:pmid:32426333", "type": "manuscript", "label": "PMID 32426333 full text"}, {"id": "data:geo:GSE30153", "type": "dataset", "label": "GEO GSE30153"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32426333", "type": "extraction", "used": ["source:pmid:32426333"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30153", "type": "accession_resolution", "used": ["data:geo:GSE30153"], "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:32426333", "parent_hash": "sha256:f00631c03e41bf0e8d5e38a65e2aff11f89325a685d1daac98dcc55a89c86222", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE30153 licence not read", "asset:data:geo:GSE30153 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "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": ["es the gene expression profiling data of the microarray dataset GSE30153 from the Gene Expression Om"], "order_basis": "paper_text_order:726", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}