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pmid:36685554
Investigating regulatory patterns of NLRP3 Inflammasome features and association with immune microenvironment in Crohn's disease.
Huihuan Wu · Ruijie Zeng · Xinqi Qiu · Kequan Chen · Zewei Zhuo · Kehang Guo · Yawen Xiang · Qi Yang · Rui Jiang · Felix W Leung · Qizhou Lian · Weihong Sha · Hao Chen
Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.1096587
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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The role of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in Crohn's disease remains largely unknown.\nMethods: The microarray-based transcriptomic data and corresponding clinical information of GSE100833 and GSE16879 were obtained from the Gene Expression Omnibus (GEO) database. Identification of in the NLRP3 inflammasome-related genes and construction of LASSO regression model. Immune landscape analysis was evaluated with ssGSEA. Classification of Crohn's-disease samples based on NLRP3 inflammasome-related genes with ConsensusClusterPlus. Functional enrichment analysis, gene set variation analysis (GSVA) and drug-gene interaction network.\nResults: The expressions of NLRP3 inflammasome-related genes were increased in diseased tissues, and higher expressions of NLRP3 inflammasome-related genes were correlated with generally enhanced immune cell infiltration, immune-related pathways and human leukocyte antigen (HLA)-gene expressions. The gene-based signature showed well performance in the diagnosis of Crohn's disease. Moreover, consensus clustering identified two Crohn's disease clusters based on NLRP3 inflammasome-related genes, and cluster 2 was with higher expressions of the genes. Cluster 2 demonstrated upregulated activities of immune environment in Crohn's disease. Furthermore, four key hub genes were identified and potential drugs were explored for the treatment of Crohn's disease.\nConclusions: Our findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn's disease from transcriptomic aspects. These findings provide in silico insights into the diagnosis and treatment of Crohn's disease and might assist in the clinical decision-making process.", "claims": [{"id": "claim-method", "statement": "For the GSE100833 data and GSE16879 data, we first used Wilcoxon test to analyze the expression of NLRP3 inflammasome-related genes between the diseased samples and normal tissues. The DEGs were further identified by the limma package (15) with the threshold of adjusted P < 0.05 between the diseased samples and normal tissues. Volcano plots and heatmaps were used to demonstrate the expressions of DEGs between the two groups. The DEGs that were associated with Crohn’s disease development were further sorted by univariate logistic regression analysis. LASSO cox regression was performed by the glmnet package to remove redundant genes and construct a refined model (16).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36685554", "locator": "sections[5] \"Identification of differentially expressed genes in the NLRP3 inflammasome-related genes and construction of LASSO regression model\" paragraph 2", "quote": "For the GSE100833 data and GSE16879 data, we first used Wilcoxon test to analyze the expression of NLRP3 inflammasome-related genes between the diseased samples and normal tissues. The DEGs were further identified by the limma package (15) with the threshold of adjusted P < 0.05 between the diseased samples and normal tissues. Volcano plots and heatmaps were used to demonstrate the expressions of DEGs between the two groups. The DEGs that were associated with Crohn’s disease development were further sorted by univariate logistic regression analysis. LASSO cox regression was performed by the glmnet package to remove redundant genes and construct a refined model (16)."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36685554", "locator": "sections[22] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36685554", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Our findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects.", "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:36685554"], "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:GSE100833"], "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:GSE100833"], "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:36685554", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.1096587", "sha256": "sha256:d9728f0bf290d1ac0108742eed3cecab1bc811b34e30a0183f9fa3e690b724c3", "bytes": 32863, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.1096587", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9849378", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100833", "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=GSE100833", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100833", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . 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"GSM3260368", "GSM3260369", "GSM3260370", "GSM3260371", "GSM3260372", "GSM3260373", "GSM3260374", "GSM3260375", "GSM3260376", "GSM3260377", "GSM3260378", "GSM3260379", "GSM3260380", "GSM3260381", "GSM3260382", "GSM3260383", "GSM3260384", "GSM3260385", "GSM3260386", "GSM3260387", "GSM3260388", "GSM3260389", "GSM3260390", "GSM3260391", "GSM3260392", "GSM3260393", "GSM3260394", "GSM3260395", "GSM3260396", "GSM3260397", "GSM3260398", "GSM3260399", "GSM3260400", "GSM3260401", "GSM3260402", "GSM3260403", "GSM3260404", "GSM3260405", "GSM3260406", "GSM3260407", "GSM3260408", "GSM3260409", "GSM3260410", "GSM3260411", "GSM3260412", "GSM3260413", "GSM3260414", "GSM3260415", "GSM3260416", "GSM3260417", "GSM3260418", "GSM3260419", "GSM3260420", "GSM3260421", "GSM3260422", "GSM3260423", "GSM3260424", "GSM3260425", "GSM3260426", "GSM3260427", "GSM3260428", "GSM3260429", "GSM3260430", "GSM3260431", "GSM3260432", "GSM3260433", "GSM3260434", "GSM3260435", "GSM3260436", "GSM3260437", "GSM3260438", "GSM3260439", "GSM3260440", "GSM3260441", "GSM3260442", "GSM3260443", "GSM3260444", "GSM3260445", "GSM3260446", "GSM3260447", "GSM3260448", "GSM3260449", "GSM3260450", "GSM3260451", "GSM3260452", "GSM3260453", "GSM3260454", "GSM3260455", "GSM3260456", "GSM3260457", "GSM3260458", "GSM3260459", "GSM3260460", "GSM3260461", "GSM3260462", "GSM3260463", "GSM3260464", "GSM3260465", "GSM3260466", "GSM3260467", "GSM3260468", "GSM3260469", "GSM3260470", "GSM3260471", "GSM3260472", "GSM3260473", "GSM3260474", "GSM3260475", "GSM3260476", "GSM3260477", "GSM3260478", "GSM3260479", "GSM3260480", "GSM3260481", "GSM3260482", "GSM3260483", "GSM3260484", "GSM3260485", "GSM3260486", "GSM3260487", "GSM3260488", "GSM3260489", "GSM3260490", "GSM3260491", "GSM3260492", "GSM3260493", "GSM3260494", "GSM3260495", "GSM3260496", "GSM3260497", "GSM3260498", "GSM3260499", "GSM3260500", "GSM3260501", "GSM3260502", "GSM3260503", "GSM3260504", "GSM3260505", "GSM3260506", "GSM3260507", "GSM3260508", "GSM3260509", "GSM3260510", "GSM3260511", "GSM3260512", "GSM3260513", "GSM3260514", "GSM3260515", "GSM3260516", "GSM3260517", "GSM3260518", "GSM3260519", "GSM3260520", "GSM3260521", "GSM3260522", "GSM3260523", "GSM3260524", "GSM3260525", "GSM3260526", "GSM3260527", "GSM3260528", "GSM3260529", "GSM3260530", "GSM3260531", "GSM3260532", "GSM3260533", "GSM3260534", "GSM3260535", "GSM3260536", "GSM3260537", "GSM3260538", "GSM3260539", "GSM3260540", "GSM3260541", "GSM3260542", "GSM3260543", "GSM3260544", "GSM3260545", "GSM3260546", "GSM3260547", "GSM3260548", "GSM3260549", "GSM3260550", "GSM3260551", "GSM3260552", "GSM3260553", "GSM3260554", "GSM3260555", "GSM3260556", "GSM3260557", "GSM3260558", "GSM3260559", "GSM3260560", "GSM3260561", "GSM3260562", "GSM3260563", "GSM3260564", "GSM3260565", "GSM3260566", "GSM3260567", "GSM3260568", "GSM3260569", "GSM3260570", "GSM3260571", "GSM3260572", "GSM3260573", "GSM3260574", "GSM3260575", "GSM3260576", "GSM3260577", "GSM3260578", "GSM3260579", "GSM3260580", "GSM3260581", "GSM3260582", "GSM3260583", "GSM3260584", "GSM3260585", "GSM3260586", "GSM3260587", "GSM3260588", "GSM3260589", "GSM3260590", "GSM3260591", "GSM3260592", "GSM3260593", "GSM3260594", "GSM3260595", "GSM3260596", "GSM3260597", "GSM3260598", "GSM3260599", "GSM3260600", "GSM3260601", "GSM3260602", "GSM3260603", "GSM3260604", "GSM3260605", "GSM3260606", "GSM3260607", "GSM3260608", "GSM3260609", "GSM3260610", "GSM3260611", "GSM3260612", "GSM3260613", "GSM3260614", "GSM3260615", "GSM3260616", "GSM3260617", "GSM3260618", "GSM3260619", "GSM3260620", "GSM3260621", "GSM3260622", "GSM3260623", "GSM3260624", "GSM3260625", "GSM3260626", "GSM3260627", "GSM3260628", "GSM3260629", "GSM3260630", "GSM3260631", "GSM3260632", "GSM3260633", "GSM3260634", "GSM3260635", "GSM3260636", "GSM3260637", "GSM3260638", "GSM3260639", "GSM3260640", "GSM3260641", "GSM3260642", "GSM3260643", "GSM3260644", "GSM3260645", "GSM3260646", "GSM3260647", "GSM3260648", "GSM3260649", "GSM3260650", "GSM3260651", "GSM3260652", "GSM3260653", "GSM3260654", "GSM3260655", "GSM3260656", "GSM3260657", "GSM3260658", "GSM3260659", "GSM3260660", "GSM3260661", "GSM3260662", "GSM3260663", "GSM3260664", "GSM3260665", "GSM3260666", "GSM3260667", "GSM3260668", "GSM3260669", "GSM3260670", "GSM3260671", "GSM3260672", "GSM3260673", "GSM3260674", "GSM3260675", "GSM3260676", "GSM3260677", "GSM3260678", "GSM3260679", "GSM3260680", "GSM3260681", "GSM3260682", "GSM3260683", "GSM3260684", "GSM3260685", "GSM3260686", "GSM3260687", "GSM3260688", "GSM3260689", "GSM3260690", "GSM3260691", "GSM3260692", "GSM3260693", "GSM3260694", "GSM3260695", "GSM3260696", "GSM3260697", "GSM3260698", "GSM3260699", "GSM3260700", "GSM3260701", "GSM3260702", "GSM3260703", "GSM3260704", "GSM3260705", "GSM3260706", "GSM3260707", "GSM3260708", "GSM3260709", "GSM3260710", "GSM3260711", "GSM3260712", "GSM3260713", "GSM3260714", "GSM3260715", "GSM3260716", "GSM3260717", "GSM3260718", "GSM3260719", "GSM3260720", "GSM3260721", "GSM3260722", "GSM3260723", "GSM3260724", "GSM3260725", "GSM3260726", "GSM3260727", "GSM3260728", "GSM3260729", "GSM3260730", "GSM3260731", "GSM3260732", "GSM3260733", "GSM3260734", "GSM3260735", "GSM3260736", "GSM3260737", "GSM3260738", "GSM3260739", "GSM3260740", "GSM3260741", "GSM3260742", "GSM3260743", "GSM3260744", "GSM3260745", "GSM3260746", "GSM3260747", "GSM3260748", "GSM3260749", "GSM3260750", "GSM3260751", "GSM3260752", "GSM3260753", "GSM3260754", "GSM3260755", "GSM3260756", "GSM3260757", "GSM3260758", "GSM3260759", "GSM3260760", "GSM3260761", "GSM3260762", "GSM3260763", "GSM3260764", "GSM3260765", "GSM3260766", "GSM3260767", "GSM3260768", "GSM3260769", "GSM3260770", "GSM3260771", "GSM3260772", "GSM3260773", "GSM3260774", "GSM3260775", "GSM3260776", "GSM3260777", "GSM3260778", "GSM3260779", "GSM3260780", "GSM3260781", "GSM3260782", "GSM3260783", "GSM3260784", "GSM3260785", "GSM3260786", "GSM3260787", "GSM3260788", "GSM3260789", "GSM3260790", "GSM3260791", "GSM3260792", "GSM3260793", "GSM3260794", "GSM3260795", "GSM3260796", "GSM3260797", "GSM3260798", "GSM3260799", "GSM3260800", "GSM3260801", "GSM3260802", "GSM3260803", "GSM3260804", "GSM3260805", "GSM3260806", "GSM3260807", "GSM3260808", "GSM3260809", "GSM3260810", "GSM3260811", "GSM3260812", "GSM3260813", "GSM3260814", "GSM3260815", "GSM3260816", "GSM3260817", "GSM3260818", "GSM3260819", "GSM3260820", "GSM3260821", "GSM3260822", "GSM3260823", "GSM3260824", "GSM3260825", "GSM3260826", "GSM3260827", "GSM3260828", "GSM3260829", "GSM3260830", "GSM3260831", "GSM3260832", "GSM3260833", "GSM3260834", "GSM3260835", "GSM3260836", "GSM3260837", "GSM3260838", "GSM3260839", "GSM3260840", "GSM3260841", "GSM3260842", "GSM3260843", "GSM3260844", "GSM3260845", "GSM3260846", "GSM3260847", "GSM3260848", "GSM3260849", "GSM3260850", "GSM3260851", "GSM3260852", "GSM3260853", "GSM3260854", "GSM3260855", "GSM3260856", "GSM3260857", "GSM3260858", "GSM3260859", "GSM3260860", "GSM3260861", "GSM3260862", "GSM3260863", "GSM3260864", "GSM3260865", "GSM3260866", "GSM3260867", "GSM3260868", "GSM3260869", "GSM3260870", "GSM3260871", "GSM3260872", "GSM3260873", "GSM3260874", "GSM3260875", "GSM3260876", "GSM3260877", "GSM3260878", "GSM3260879", "GSM3260880", "GSM3260881", "GSM3260882", "GSM3260883", "GSM3260884", "GSM3260885", "GSM3260886", "GSM3260887", "GSM3260888", "GSM3260889", "GSM3260890", "GSM3260891", "GSM3260892", "GSM3260893", "GSM3260894", "GSM3260895", "GSM3260896", "GSM3260897", "GSM3260898", "GSM3260899", "GSM3260900", "GSM3260901", "GSM3260902", "GSM3260903", "GSM3260904", "GSM3260905", "GSM3260906", "GSM3260907", "GSM3260908", "GSM3260909", "GSM3260910", "GSM3260911", "GSM3260912", "GSM3260913", "GSM3260914", "GSM3260915", "GSM3260916", "GSM3260917", "GSM3260918", "GSM3260919", "GSM3260920", "GSM3260921", "GSM3260922", "GSM3260923", "GSM3260924", "GSM3260925", "GSM3260926", "GSM3260927", "GSM3260928", "GSM3260929", "GSM3260930", "GSM3260931", "GSM3260932", "GSM3260933", "GSM3260934", "GSM3260935", "GSM3260936", "GSM3260937", "GSM3260938", "GSM3260939", "GSM3260940", "GSM3260941", "GSM3260942", "GSM3260943", "GSM3260944", "GSM3260945", "GSM3260946", "GSM3260947", "GSM3260948", "GSM3260949", "GSM3260950", "GSM3260951", "GSM3260952", "GSM3260953", "GSM3260954", "GSM3260955", "GSM3260956", "GSM3260957", "GSM3260958", "GSM3260959", "GSM3260960", "GSM3260961", "GSM3260962", "GSM3260963", "GSM3260964", "GSM3260965", "GSM3260966", "GSM3260967", "GSM3260968", "GSM3260969", "GSM3260970", "GSM3260971", "GSM3260972", "GSM3260973", "GSM3260974", "GSM3260975", "GSM3260976", "GSM3260977", "GSM3260978", "GSM3260979", "GSM3260980", "GSM3260981", "GSM3260982", "GSM3260983", "GSM3260984", "GSM3260985", "GSM3260986", "GSM3260987", "GSM3260988", "GSM3260989", "GSM3260990", "GSM3260991", "GSM3260992", "GSM3260993", "GSM3260994", "GSM3260995", "GSM3260996", "GSM3260997", "GSM3260998", "GSM3260999", "GSM3261000", "GSM3261001", "GSM3261002", "GSM3261003", "GSM3261004", "GSM3261005", "GSM3261006", "GSM3261007", "GSM3261008", "GSM3261009", "GSM3261010", "GSM3261011", "GSM3261012", "GSM3261013", "GSM3261014", "GSM3261015", "GSM3261016", "GSM3261017", "GSM3261018", "GSM3261019", "GSM3261020", "GSM3261021", "GSM3261022", "GSM3261023", "GSM3261024", "GSM3261025", "GSM3261026", "GSM3261027", "GSM3261028", "GSM3261029", "GSM3261030", "GSM3261031", "GSM3261032", "GSM3261033", "GSM3261034", "GSM3261035", "GSM3261036", "GSM3261037", "GSM3261038", "GSM3261039", "GSM3261040", "GSM3261041", "GSM3261042", "GSM3261043", "GSM3261044", "GSM3261045", "GSM3261046", "GSM3261047", "GSM3261048", "GSM3261049", "GSM3261050", "GSM3261051", "GSM3261052", "GSM3261053", "GSM3261054", "GSM3261055", "GSM3261056", "GSM3261057", "GSM3261058", "GSM3261059", "GSM3261060", "GSM3261061", "GSM3261062", "GSM3261063", "GSM3261064", "GSM3261065", "GSM3261066", "GSM3261067", "GSM3261068", "GSM3261069", "GSM3261070", "GSM3261071", "GSM3261072", "GSM3261073", "GSM3261074", "GSM3261075", "GSM3261076", "GSM3261077", "GSM3261078", "GSM3261079", "GSM3261080", "GSM3261081", "GSM3261082", "GSM3261083", "GSM3261084", "GSM3261085", "GSM3261086", "GSM3261087", "GSM3261088", "GSM3261089", "GSM3261090", "GSM3261091", "GSM3261092", "GSM3261093", "GSM3261094", "GSM3261095", "GSM3261096", "GSM3261097", "GSM3261098", "GSM3261099", "GSM3261100", "GSM3261101", "GSM3261102", "GSM3261103", "GSM3261104", "GSM3261105", "GSM3261106", "GSM3261107", "GSM3261108", "GSM3261109", "GSM3261110", "GSM3261111", "GSM3261112", "GSM3261113", "GSM3261114", "GSM3261115", "GSM3261116", "GSM3261117", "GSM3261118", "GSM3261119", "GSM3261120", "GSM3261121", "GSM3261122", "GSM3261123", "GSM3261124", "GSM3261125", "GSM3261126", "GSM3261127", "GSM3261128", "GSM3261129", "GSM3261130", "GSM3261131", "GSM3261132", "GSM3261133", "GSM3261134", "GSM3261135", "GSM3261136", "GSM3261137", "GSM3261138", "GSM3261139", "GSM3261140", "GSM3261141", "GSM3261142", "GSM3261143", "GSM3261144", "GSM3261145", "GSM3261146", "GSM3261147", "GSM3261148", "GSM3261149", "GSM3261150", "GSM3261151", "GSM3261152", "GSM3261153", "GSM3261154", "GSM3261155", "GSM3261156", "GSM3261157", "GSM3261158", "GSM3261159", "GSM3261160", "GSM3261161", "GSM3261162", "GSM3261163", "GSM3261164", "GSM3261165", "GSM3261166", "GSM3261167", "GSM3261168", "GSM3261169", "GSM3261170", "GSM3261171", "GSM3261172", "GSM3261173", "GSM3261174", "GSM3261175", "GSM3261176", "GSM3261177", "GSM3261178", "GSM3261179", "GSM3261180", "GSM3261181", "GSM3261182", "GSM3261183", "GSM3261184", "GSM3261185", "GSM3261186", "GSM3261187", "GSM3261188", "GSM3261189", "GSM3261190", "GSM3261191", "GSM3261192", "GSM3261193", "GSM3261194", "GSM3261195", "GSM3261196", "GSM3261197", "GSM3261198", "GSM3261199", "GSM3261200", "GSM3261201", "GSM3261202", "GSM3261203", "GSM3261204", "GSM3261205", "GSM3261206", "GSM3261207", "GSM3261208", "GSM3261209", "GSM3261210", "GSM3261211", "GSM3261212", "GSM3261213", "GSM3261214", "GSM3261215", "GSM3261216", "GSM3261217", "GSM3261218", "GSM3261219", 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