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pmid:37700362
Identification and validation of core genes for type 2 diabetes mellitus by integrated analysis of single-cell and bulk RNA-sequencing.
Tingting Yang · Chaoying Yan · Lan Yang · Jialu Tan · Shiqiu Jiang · Juan Hu · Wei Gao · Qiang Wang · Yansong Li
European journal of medical research · 2023 doi:10.1186/s40001-023-01321-1
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Complete file
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We intended to authenticate critical genes linked to T2DM progression by tandem single-cell sequencing and general transcriptome sequencing data.\nMETHODS: T2DM single-cell RNA-sequencing data were submitted by the Gene Expression Omnibus (GEO) database and ArrayExpress (EBI), from which gene expression matrices were retrieved. The common cell clusters and representative marker genes were ascertained by principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), CellMarker, and FindMarkers in two datasets (GSE86469 and GSE81608). T2DM-related differentially expressed marker genes were defined by intersection analysis of marker genes and GSE86468-differentially expressed genes. Receiver operating characteristic (ROC) curves were utilized to assign representative marker genes with diagnostic values by GSE86468, GSE29226 and external validation GSE29221, and their prospective target compounds were forecasted by PubChem. Besides, the R package clusterProfiler-based functional annotation was designed to unveil the intrinsic mechanisms of the target genes. At last, western blot was used to validate the alternation of CDKN1C and DLK1 expression in primary pancreatic islet cells cultured with or without 30mM glucose.\nRESULTS: Three common cell clusters were authenticated in two independent T2DM single-cell sequencing data, covering neurons, epithelial cells, and smooth muscle cells. Functional ensemble analysis disclosed an intimate association of these cell clusters with peptide/insulin secretion and pancreatic development. Pseudo-temporal trajectory analysis indicated that almost all epithelial and smooth muscle cells were of neuron origin. We characterized CDKN1C and DLK1, which were notably upregulated in T2DM samples, with satisfactory availability in recognizing three representative marker genes in non-diabetic and T2DM samples, and they were also robustly interlinked with the clinical characteristics of patients. Western blot also demonstrated that, compared with control group, the expression of CDKN1C and DLK1 were increased in primary pancreatic islet cells cultured with 30 mM glucose for 48 h. Additionally, PubChem projected 11 and 21 potential compounds for CDKN1C and DLK1, respectively.\nCONCLUSION: It is desirable that the emergence of the 2 critical genes indicated (CDKN1C and DLK1) could be catalysts for the investigation of the mechanisms of T2DM progression and the exploitation of innovative therapies.", "claims": [{"id": "claim-method", "statement": "Briefly, the expression profiles of the T2DM-related DEMGs in the GSE86468 and GSE29226 datasets were matched, the ROC curves of the corresponding genes were plotted and the AUCs were calculated by R package pROC in both datasets [57].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37700362", "locator": "sections[24] \"ROC curve-based assessment of diagnostic benefit\" paragraph 2", "quote": "Briefly, the expression profiles of the T2DM-related DEMGs in the GSE86468 and GSE29226 datasets were matched, the ROC curves of the corresponding genes were plotted and the AUCs were calculated by R package pROC in both datasets [57]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37700362", "locator": "sections[33] \"Availability of data and materials\" paragraph 2", "quote": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results revealed that CDKN1C and DLK1 had favorable sample discrimination in both datasets (both AUC > 0.75; Fig. 6A) and considered as critical genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37700362", "locator": "sections[9] \"Assessment of the diagnostic value and clinical relevance of the T2DM-related DEMGs\" paragraph 2", "quote": "The results revealed that CDKN1C and DLK1 had favorable sample discrimination in both datasets (both AUC > 0.75; Fig. 6A) and considered as critical genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The results revealed that CDKN1C and DLK1 had favorable sample discrimination in both datasets (both AUC > 0.75; Fig. 6A) and considered as critical genes.", "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:37700362"], "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:E-MTAB-5061"], "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:E-MTAB-5061"], "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:37700362", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s40001-023-01321-1", "sha256": "sha256:7c40348ef5e49e83a95f9d519f11a9b8768552c29d8faf9fd101aa6ecd44524f", "bytes": 68528, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s40001-023-01321-1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10498638", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-5061", "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=E-MTAB-5061", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-5061", "version": null, "note": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). 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The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM722668", "GSM722669", "GSM722670", "GSM722671", "GSM722672", "GSM722673", "GSM722674", "GSM722675", "GSM722676", "GSM722677", "GSM722678", "GSM722679", "GSM722680", "GSM722681", "GSM722682", "GSM722683", "GSM722684", "GSM722685", "GSM722686", "GSM722687", "GSM722688", "GSM722689", "GSM722690", "GSM722691"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "6947", "taxon": "Homo sapiens", "title": "Global Gene Expression Profiles of Skeletal Muscle in Males with Type 2 Diabetes.", "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:GSE29226", "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=GSE29226", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE29226", "version": null, "note": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). 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"GSM2158098", "GSM2158099", "GSM2158100", "GSM2158101", "GSM2158102", "GSM2158103", "GSM2158104", "GSM2158105", "GSM2158106", "GSM2158107", "GSM2158108", "GSM2158109", "GSM2158110", "GSM2158111", "GSM2158112", "GSM2158113", "GSM2158114", "GSM2158115", "GSM2158116", "GSM2158117", "GSM2158118", "GSM2158119", "GSM2158120", "GSM2158121", "GSM2158122", "GSM2158123", "GSM2158124", "GSM2158125", "GSM2158126", "GSM2158127", "GSM2158128", "GSM2158129", "GSM2158130", "GSM2158131", "GSM2158132", "GSM2158133", "GSM2158134", "GSM2158135", "GSM2158136", "GSM2158137", "GSM2158138", "GSM2158139", "GSM2158140", "GSM2158141", "GSM2158142", "GSM2158143", "GSM2158144", "GSM2158145", "GSM2158146", "GSM2158147", "GSM2158148", "GSM2158149", "GSM2158150", "GSM2158151", "GSM2158152", "GSM2158153", "GSM2158154", "GSM2158155", "GSM2158156", "GSM2158157", "GSM2158158", "GSM2158159", "GSM2158160", "GSM2158161", "GSM2158162", "GSM2158163", "GSM2158164", "GSM2158165", "GSM2158166", "GSM2158167", "GSM2158168", "GSM2158169", "GSM2158170", "GSM2158171", "GSM2158172", "GSM2158173", "GSM2158174", "GSM2158175", "GSM2158176", "GSM2158177", "GSM2158178", "GSM2158179", "GSM2158180", "GSM2158181", "GSM2158182", "GSM2158183", "GSM2158184", "GSM2158185", "GSM2158186", "GSM2158187", "GSM2158188", "GSM2158189", "GSM2158190", "GSM2158191", "GSM2158192", "GSM2158193", "GSM2158194", "GSM2158195", "GSM2158196", "GSM2158197", "GSM2158198", "GSM2158199", "GSM2158200", "GSM2158201", "GSM2158202", "GSM2158203", "GSM2158204", "GSM2158205", "GSM2158206", "GSM2158207", "GSM2158208", "GSM2158209", "GSM2158210", "GSM2158211", "GSM2158212", "GSM2158213", "GSM2158214", "GSM2158215", "GSM2158216", "GSM2158217", "GSM2158218", "GSM2158219", "GSM2158220", "GSM2158221", "GSM2158222", "GSM2158223", "GSM2158224", "GSM2158225", "GSM2158226", "GSM2158227", "GSM2158228", "GSM2158229", "GSM2158230", "GSM2158231", "GSM2158232", "GSM2158233", "GSM2158234", "GSM2158235", "GSM2158236", "GSM2158237", "GSM2158238", "GSM2158239", "GSM2158240", "GSM2158241", "GSM2158242", "GSM2158243", "GSM2158244", "GSM2158245", "GSM2158246", "GSM2158247", "GSM2158248", "GSM2158249", "GSM2158250", "GSM2158251", "GSM2158252", "GSM2158253", "GSM2158254", "GSM2158255", "GSM2158256", "GSM2158257", "GSM2158258", "GSM2158259", "GSM2158260", "GSM2158261", "GSM2158262", "GSM2158263", "GSM2158264", "GSM2158265", "GSM2158266", "GSM2158267", "GSM2158268", "GSM2158269", "GSM2158270", "GSM2158271", "GSM2158272", "GSM2158273", "GSM2158274", "GSM2158275", "GSM2158276", "GSM2158277", "GSM2158278", "GSM2158279", "GSM2158280", "GSM2158281", "GSM2158282", "GSM2158283", "GSM2158284", "GSM2158285", "GSM2158286", "GSM2158287", "GSM2158288", "GSM2158289", "GSM2158290", "GSM2158291", "GSM2158292", "GSM2158293", "GSM2158294", "GSM2158295", "GSM2158296", "GSM2158297", "GSM2158298", "GSM2158299", "GSM2158300", "GSM2158301", "GSM2158302", "GSM2158303", "GSM2158304", "GSM2158305", "GSM2158306", "GSM2158307", "GSM2158308", "GSM2158309", "GSM2158310", "GSM2158311", "GSM2158312", "GSM2158313", "GSM2158314", "GSM2158315", "GSM2158316", "GSM2158317", "GSM2158318", "GSM2158319", "GSM2158320", "GSM2158321", "GSM2158322", "GSM2158323", "GSM2158324", "GSM2158325", "GSM2158326", "GSM2158327", "GSM2158328", "GSM2158329", "GSM2158330", "GSM2158331", "GSM2158332", "GSM2158333", "GSM2158334", "GSM2158335", "GSM2158336", "GSM2158337", "GSM2158338", "GSM2158339", "GSM2158340", "GSM2158341", "GSM2158342", "GSM2158343", "GSM2158344", "GSM2158345", "GSM2158346", "GSM2158347", "GSM2158348", "GSM2158349", "GSM2158350", "GSM2158351", "GSM2158352", "GSM2158353", "GSM2158354", "GSM2158355", "GSM2158356", "GSM2158357", "GSM2158358", "GSM2158359", "GSM2158360", "GSM2158361", "GSM2158362", "GSM2158363", "GSM2158364", "GSM2158365", "GSM2158366", "GSM2158367", "GSM2158368", "GSM2158369", "GSM2158370", "GSM2158371", "GSM2158372", "GSM2158373", "GSM2158374", "GSM2158375", "GSM2158376", "GSM2158377", "GSM2158378", "GSM2158379", "GSM2158380", "GSM2158381", "GSM2158382", "GSM2158383", "GSM2158384", "GSM2158385", "GSM2158386", "GSM2158387", "GSM2158388", "GSM2158389", "GSM2158390", "GSM2158391", "GSM2158392", "GSM2158393", "GSM2158394", "GSM2158395", "GSM2158396", "GSM2158397", "GSM2158398", "GSM2158399", "GSM2158400", "GSM2158401", "GSM2158402", "GSM2158403", "GSM2158404", "GSM2158405", "GSM2158406", "GSM2158407", "GSM2158408", "GSM2158409", "GSM2158410", "GSM2158411", "GSM2158412", "GSM2158413", "GSM2158414", "GSM2158415", "GSM2158416", "GSM2158417", "GSM2158418", "GSM2158419", "GSM2158420", "GSM2158421", "GSM2158422", "GSM2158423", "GSM2158424", "GSM2158425", "GSM2158426", "GSM2158427", "GSM2158428", "GSM2158429", "GSM2158430", "GSM2158431", "GSM2158432", "GSM2158433", "GSM2158434", "GSM2158435", "GSM2158436", "GSM2158437", "GSM2158438", "GSM2158439", "GSM2158440", "GSM2158441", "GSM2158442", "GSM2158443", "GSM2158444", "GSM2158445", "GSM2158446", "GSM2158447", "GSM2158448", "GSM2158449", "GSM2158450", "GSM2158451", "GSM2158452", "GSM2158453", "GSM2158454", "GSM2158455", "GSM2158456", "GSM2158457", "GSM2158458", "GSM2158459", "GSM2158460", "GSM2158461", "GSM2158462", "GSM2158463", "GSM2158464", "GSM2158465", "GSM2158466", "GSM2158467", "GSM2158468", "GSM2158469", "GSM2158470", "GSM2158471", "GSM2158472", "GSM2158473", "GSM2158474", "GSM2158475", "GSM2158476", "GSM2158477", "GSM2158478", "GSM2158479", "GSM2158480", "GSM2158481", "GSM2158482", "GSM2158483", "GSM2158484", "GSM2158485", "GSM2158486", "GSM2158487", "GSM2158488", "GSM2158489", "GSM2158490", "GSM2158491", "GSM2158492", "GSM2158493", "GSM2158494", "GSM2158495", "GSM2158496", "GSM2158497", "GSM2158498", "GSM2158499", "GSM2158500", "GSM2158501", "GSM2158502", "GSM2158503", "GSM2158504", "GSM2158505", "GSM2158506", "GSM2158507", "GSM2158508", "GSM2158509", "GSM2158510", "GSM2158511", "GSM2158512", "GSM2158513", "GSM2158514", "GSM2158515", "GSM2158516", "GSM2158517", "GSM2158518", "GSM2158519", "GSM2158520", "GSM2158521", "GSM2158522", "GSM2158523", "GSM2158524", "GSM2158525", "GSM2158526", "GSM2158527", "GSM2158528", "GSM2158529", "GSM2158530", "GSM2158531", "GSM2158532", "GSM2158533", "GSM2158534", "GSM2158535", "GSM2158536", "GSM2158537", "GSM2158538", "GSM2158539", "GSM2158540", "GSM2158541", "GSM2158542", "GSM2158543", "GSM2158544", "GSM2158545", "GSM2158546", "GSM2158547", "GSM2158548", "GSM2158549", "GSM2158550", "GSM2158551", "GSM2158552", "GSM2158553", "GSM2158554", "GSM2158555", "GSM2158556", "GSM2158557", "GSM2158558", "GSM2158559", "GSM2158560", "GSM2158561", "GSM2158562", "GSM2158563", "GSM2158564", "GSM2158565", "GSM2158566", "GSM2158567", "GSM2158568", "GSM2158569", "GSM2158570", "GSM2158571", "GSM2158572", "GSM2158573", "GSM2158574", "GSM2158575", "GSM2158576", "GSM2158577", "GSM2158578", "GSM2158579", "GSM2158580", "GSM2158581", "GSM2158582", "GSM2158583", "GSM2158584", "GSM2158585", "GSM2158586", "GSM2158587", "GSM2158588", "GSM2158589", "GSM2158590", "GSM2158591", "GSM2158592", "GSM2158593", "GSM2158594", "GSM2158595", "GSM2158596", "GSM2158597", "GSM2158598", "GSM2158599", "GSM2158600", "GSM2158601", "GSM2158602", "GSM2158603", "GSM2158604", "GSM2158605", "GSM2158606", "GSM2158607", "GSM2158608", "GSM2158609", "GSM2158610", "GSM2158611", "GSM2158612", "GSM2158613", "GSM2158614", "GSM2158615", "GSM2158616", "GSM2158617", "GSM2158618", "GSM2158619", "GSM2158620", "GSM2158621", "GSM2158622", "GSM2158623", "GSM2158624", "GSM2158625", "GSM2158626", "GSM2158627", "GSM2158628", "GSM2158629", "GSM2158630", "GSM2158631", "GSM2158632", "GSM2158633", "GSM2158634", "GSM2158635", "GSM2158636", "GSM2158637", "GSM2158638", "GSM2158639", "GSM2158640", "GSM2158641", "GSM2158642", "GSM2158643", "GSM2158644", "GSM2158645", "GSM2158646", "GSM2158647", "GSM2158648", "GSM2158649", "GSM2158650", "GSM2158651", "GSM2158652", "GSM2158653", "GSM2158654", "GSM2158655", "GSM2158656", "GSM2158657", "GSM2158658", "GSM2158659", "GSM2158660", "GSM2158661", "GSM2158662", "GSM2158663", "GSM2158664", "GSM2158665", "GSM2158666", "GSM2158667", "GSM2158668", "GSM2158669", "GSM2158670", "GSM2158671", "GSM2158672", "GSM2158673", "GSM2158674", "GSM2158675", "GSM2158676", "GSM2158677", "GSM2158678", "GSM2158679", "GSM2158680", "GSM2158681", "GSM2158682", "GSM2158683", "GSM2158684", "GSM2158685", "GSM2158686", "GSM2158687", "GSM2158688", "GSM2158689", "GSM2158690", "GSM2158691", "GSM2158692", "GSM2158693", "GSM2158694", "GSM2158695", "GSM2158696", "GSM2158697", "GSM2158698", "GSM2158699", "GSM2158700", "GSM2158701", "GSM2158702", "GSM2158703", "GSM2158704", "GSM2158705", "GSM2158706", "GSM2158707", "GSM2158708", "GSM2158709", "GSM2158710", "GSM2158711", "GSM2158712", "GSM2158713", "GSM2158714", "GSM2158715", "GSM2158716", "GSM2158717", "GSM2158718", "GSM2158719", "GSM2158720", "GSM2158721", "GSM2158722", "GSM2158723", "GSM2158724", "GSM2158725", "GSM2158726", "GSM2158727", "GSM2158728", "GSM2158729", "GSM2158730", "GSM2158731", "GSM2158732", "GSM2158733", "GSM2158734", "GSM2158735", "GSM2158736", "GSM2158737", "GSM2158738", "GSM2158739", "GSM2158740", "GSM2158741", "GSM2158742", "GSM2158743", "GSM2158744", "GSM2158745", "GSM2158746", "GSM2158747", "GSM2158748", "GSM2158749", "GSM2158750", "GSM2158751", "GSM2158752", "GSM2158753", "GSM2158754", "GSM2158755", "GSM2158756", "GSM2158757", "GSM2158758", "GSM2158759", "GSM2158760", "GSM2158761", "GSM2158762", "GSM2158763", "GSM2158764", "GSM2158765", "GSM2158766", "GSM2158767", "GSM2158768", "GSM2158769", "GSM2158770", "GSM2158771", "GSM2158772", "GSM2158773", "GSM2158774", "GSM2158775", "GSM2158776", "GSM2158777", "GSM2158778", "GSM2158779", "GSM2158780", "GSM2158781", "GSM2158782", "GSM2158783", "GSM2158784", "GSM2158785", "GSM2158786", "GSM2158787", "GSM2158788", "GSM2158789", "GSM2158790", "GSM2158791", "GSM2158792", "GSM2158793", "GSM2158794", "GSM2158795", "GSM2158796", "GSM2158797", "GSM2158798", "GSM2158799", "GSM2158800", "GSM2158801", "GSM2158802", "GSM2158803", "GSM2158804", "GSM2158805", "GSM2158806", "GSM2158807", "GSM2158808", "GSM2158809", "GSM2158810", "GSM2158811", "GSM2158812", "GSM2158813", "GSM2158814", "GSM2158815", "GSM2158816", "GSM2158817", "GSM2158818", "GSM2158819", "GSM2158820", "GSM2158821", "GSM2158822", "GSM2158823", "GSM2158824", "GSM2158825", "GSM2158826", "GSM2158827", "GSM2158828", "GSM2158829", "GSM2158830", "GSM2158831", "GSM2158832", "GSM2158833", "GSM2158834", "GSM2158835", "GSM2158836", "GSM2158837", "GSM2158838", "GSM2158839", "GSM2158840", "GSM2158842", "GSM2158843", "GSM2158844", "GSM2158846", "GSM2158848", "GSM2158849", "GSM2158850", "GSM2158852", "GSM2158853", "GSM2158855", "GSM2158856", "GSM2158858", "GSM2158859", "GSM2158861", "GSM2158862", "GSM2158863", "GSM2158865", "GSM2158866", "GSM2158868", "GSM2158869", "GSM2158871", "GSM2158872", "GSM2158874", "GSM2158875", "GSM2158877", "GSM2158878", "GSM2158879", "GSM2158881", "GSM2158882", "GSM2158884", "GSM2158885", "GSM2158887", "GSM2158888", "GSM2158889", "GSM2158891", "GSM2158892", "GSM2158894", "GSM2158895", "GSM2158896", "GSM2158898", "GSM2158899", "GSM2158901", "GSM2158902", "GSM2158904", "GSM2158906", "GSM2158907", "GSM2158908", "GSM2158910", "GSM2158911", "GSM2158913", "GSM2158914", "GSM2158916", "GSM2158917", "GSM2158919", "GSM2158920", "GSM2158922", "GSM2158923", "GSM2158925", "GSM2158926", "GSM2158928", "GSM2158929", "GSM2158931", "GSM2158932", "GSM2158934", "GSM2158935", "GSM2158936", "GSM2158937", "GSM2158938", "GSM2158939", "GSM2158940", "GSM2158941", "GSM2158942", "GSM2158943", "GSM2158944", "GSM2158945", "GSM2158946", "GSM2158947", "GSM2158948", "GSM2158949", "GSM2158950", "GSM2158951", "GSM2158952", "GSM2158953", "GSM2158954", "GSM2158955", "GSM2158956", "GSM2158957", "GSM2158958", "GSM2158959", "GSM2158960", "GSM2158961", "GSM2158962", "GSM2158963", "GSM2158964", "GSM2158965", "GSM2158966", "GSM2158967", "GSM2158968", "GSM2158969", "GSM2158970", "GSM2158971", "GSM2158972", "GSM2158973", "GSM2158974", "GSM2158975", "GSM2158976", "GSM2158977", "GSM2158978", "GSM2158979", "GSM2158980", "GSM2158981", "GSM2158982", "GSM2158983", "GSM2158984", "GSM2158985", "GSM2158986", "GSM2158987", "GSM2158988", "GSM2158989", "GSM2158990", "GSM2158991", "GSM2158992", "GSM2158993", "GSM2158994", "GSM2158995", "GSM2158996", "GSM2158997", "GSM2158998", "GSM2158999", "GSM2159000", "GSM2159001", "GSM2159002", "GSM2159003", "GSM2159004", "GSM2159005", "GSM2159006", "GSM2159007", "GSM2159008", "GSM2159009", "GSM2159010", "GSM2159011", "GSM2159012", "GSM2159013", "GSM2159014", "GSM2159015", "GSM2159016", "GSM2159017", "GSM2159018", "GSM2159019", "GSM2159020", "GSM2159021", "GSM2159022", "GSM2159023", "GSM2159024", "GSM2159025", "GSM2159026", "GSM2159027", "GSM2159028", "GSM2159029", "GSM2159030", "GSM2159031", "GSM2159032", "GSM2159033", "GSM2159034", "GSM2159035", "GSM2159036", "GSM2159037", "GSM2159038", "GSM2159039", "GSM2159040", "GSM2159041", "GSM2159042", "GSM2159043", "GSM2159044", "GSM2159045", "GSM2159046", "GSM2159047", "GSM2159048", "GSM2159049", "GSM2159050", "GSM2159051", "GSM2159052", "GSM2159053", "GSM2159054", "GSM2159055", "GSM2159056", "GSM2159057", "GSM2159058", "GSM2159059", "GSM2159060", "GSM2159061", "GSM2159062", "GSM2159063", "GSM2159064", "GSM2159065", "GSM2159066", "GSM2159067", "GSM2159068", "GSM2159069", "GSM2159070", "GSM2159071", "GSM2159072", "GSM2159073", "GSM2159074", "GSM2159075", "GSM2159076", "GSM2159077", "GSM2159078", "GSM2159079", "GSM2159080", "GSM2159081", "GSM2159082", "GSM2159083", "GSM2159084", "GSM2159085", "GSM2159086", "GSM2159087", "GSM2159088", "GSM2159089", "GSM2159090", "GSM2159091", "GSM2159092", "GSM2159093", "GSM2159094", "GSM2159095", "GSM2159096", "GSM2159097", "GSM2159098", "GSM2159099", "GSM2159100", "GSM2159101", "GSM2159102", "GSM2159103", "GSM2159104", "GSM2159105", "GSM2159106", "GSM2159107", "GSM2159108", "GSM2159109", "GSM2159110", "GSM2159111", "GSM2159112", "GSM2159113", "GSM2159114", "GSM2159115", "GSM2159116", "GSM2159117", "GSM2159118", "GSM2159119", "GSM2159120", "GSM2159121", 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The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2303122", "GSM2303123", "GSM2303124", "GSM2303125", "GSM2303126", "GSM2303127", "GSM2303128", "GSM2303129", "GSM2303130", "GSM2303131", "GSM2303132", "GSM2303133", "GSM2303134", "GSM2303135", "GSM2303136", "GSM2303137", "GSM2303138", "GSM2303139", "GSM2303140", "GSM2303141", "GSM2303142", "GSM2303143", "GSM2303144", "GSM2303145"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes [bulk]", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE86469", "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=GSE86469", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE86469", "version": null, "note": "The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). 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"asset:data:geo:GSE86468 not downloaded", "asset:data:geo:GSE86468 licence not read", "asset:data:geo:GSE86469 not downloaded", "asset:data:geo:GSE86469 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": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"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": 0.7, "band": "medium", "quote": "principal component analysis"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": 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"K-means"}}, {"id": "method-6", "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": "dendrogram"}}, {"id": "method-7", "family": "image_quantification", "specific": "densitometry", "label": "Image analysis / quantification", "dsl_operations": ["segment_objects", "quantify_intensity"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["image_stack"], "evidence": {"score": 0.8, "band": "high", "quote": "Densitometr"}}, {"id": "method-8", "family": null, "specific": null, "label": "receiver operating characteristic (ROC) curve analysis using R package pROC", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Briefly, the expression profiles of the T2DM-related DEMGs in the GSE86468 and GSE29226 datasets were matched, the ROC curves of the corresponding genes were plotted and the AUCs were calculated by R package pROC in both datasets [57]."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "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": ["GSE86469", "GSE81608", "E-MTAB-5061", "GSE86468", "GSE29226", "GSE29221"], "resolved_accessions": ["GSE86469", "GSE81608", "E-MTAB-5061", "GSE86468", "GSE29226", "GSE29221"], "statements": ["The datasets [GSE86469, GSE81608, GSE86468, GSE29226 and GSE29221] for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (EBI) (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/). The related code for present study could be found on GitHub at https://github.com/liyansong1987/code-for-manuscript."], "basis": "The paper names GSE86469, GSE81608, E-MTAB-5061, GSE86468, GSE29226, GSE29221 in 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:37700362", "data:geo:E-MTAB-5061"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-5061"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:53:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 19972, "completion_tokens": 2933, "cached_tokens": 128}}, "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:37700362", "type": "paper", "label": "pmid:37700362"}, {"id": "source:pmid:37700362", "type": "manuscript", "label": "PMID 37700362 full text"}, {"id": "data:geo:E-MTAB-5061", "type": "dataset", "label": "GEO E-MTAB-5061"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37700362", "type": "paper", "label": "pmid:37700362"}, {"id": "source:pmid:37700362", "type": "manuscript", "label": "PMID 37700362 full text"}, {"id": "data:geo:E-MTAB-5061", "type": "dataset", "label": "GEO E-MTAB-5061"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37700362", "type": "extraction", "used": ["source:pmid:37700362"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-5061", "type": "accession_resolution", "used": ["data:geo:E-MTAB-5061"], "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:37700362", "parent_hash": "sha256:75d1798ba5b9aa5a021b3db01ac597ae95e4bcb8e07d94db1d8b91a062af24a0", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:E-MTAB-5061 licence not read", "asset:data:geo:E-MTAB-5061 not downloaded", "asset:data:geo:GSE29221 licence not read", "asset:data:geo:GSE29221 not downloaded", "asset:data:geo:GSE29226 licence not read", "asset:data:geo:GSE29226 not downloaded", "asset:data:geo:GSE81608 licence not read", "asset:data:geo:GSE81608 not downloaded", "asset:data:geo:GSE86468 licence not read", "asset:data:geo:GSE86468 not downloaded", "asset:data:geo:GSE86469 licence not read", "asset:data:geo:GSE86469 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["integrated analysis of single-cell and bulk RNA-sequencing.", "e sequencing data. METHODS: T2DM single-cell RNA-sequencing data were submitted by the Gene Expression O", "nalysis of T2DM-related DEMGs combining bulk RNA-seq and single cell data. A The volcano plot of", "ed DEGs by cross-tabulation analysis of bulk RNA-seq and single cell data. C GO analysis of T2DM-"], "order_basis": "paper_text_order:76", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["sic mechanisms of the target genes. At last, western blot was used to validate the alternation of CDKN", "th the clinical characteristics of patients. Western blot also demonstrated that, compared with contro", "). Expression analysis of CDKN1C and DLK1 by western blotting The expression of CDKN1C and DLK1 was furthe", "under different conditions. A Representative western blot of CDKN1C and DLK1 in primary pancreatic isl"], "order_basis": "paper_text_order:1287", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["expression in primary pancreatic islet cells cultured with or without 30mM glucose. RESULTS: Three comm", "increased in primary pancreatic islet cells cultured with 30 mM glucose for 48 h. Additionally, PubChe"], "order_basis": "paper_text_order:1401", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.642, "evidence": ["of CDKN1C and DLK1 was further confirmed in rat pancreatic islet cells. Compared with contro"], "order_basis": "paper_text_order:7048", "id": "assay:4"}, {"role": "data_generation", "definition_id": "clinical_trial", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["C and DLK1 in primary pancreatic islet cells treated with or without 30 mM glucose (HG) for 48 h. B Densitometric"], "order_basis": "paper_text_order:7377", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}