Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34760386", "kind": "science-record", "revision": 4, "content_hash": "sha256:f53dd01e5f549e2cb579df726212e65fdbde31fda7ec493d1a5132a5405b4b5e", "created_at": "2026-11-01T17:36:27Z", "updated_at": "2026-11-01T22:05:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma.", "doi": "10.7717/peerj.12394", "pmid": "34760386", "authors": ["Alice Charwudzi", "Ye Meng", "Linhui Hu", "Chen Ding", "Lianfang Pu", "Qian Li", "Mengling Xu", "Zhimin Zhai", "Shudao Xiong"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy with varied outcomes. However, the fundamental mechanisms remain to be fully defined.\nAIM: We aimed to identify core differentially co-expressed hub genes and perturbed pathways relevant to the pathogenesis and prognosis of DLBCL.\nMETHODS: We retrieved the raw gene expression profile and clinical information of GSE12453 from the Gene Expression Omnibus (GEO) database. We used integrated bioinformatics analysis to identify differentially co-expressed genes. The CIBERSORT analysis was also applied to predict tumor-infiltrating immune cells (TIICs) in the GSE12453 dataset. We performed survival and ssGSEA (single-sample Gene Set Enrichment Analysis) (for TIICs) analyses and validated the hub genes using GEPIA2 and an independent GSE31312 dataset.\nRESULTS: We identified 46 differentially co-expressed hub genes in the GSE12453 dataset. Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes. The core genes prognostic values and expression levels were further validated in the GEPIA2 database and GSE31312 dataset to be reliable (p < 0.01). The core genes' main KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichments were Ribosome and Coronavirus disease-COVID-19. High expressions of the 15 core hub genes had prognostic value in DLBCL. The core genes showed significant predictive accuracy in distinguishing DLBCL cases from non-tumor controls, with the area under the curve (AUC) ranging from 0.992 to 1.00. Finally, CIBERSORT analysis on GSE12453 revealed immune cells, including activated memory CD4+ T cells and M0, M1, and M2-macrophages as the infiltrates in the DLBCL microenvironment.\nCONCLUSION: Our study found differentially co-expressed core hub genes and relevant pathways involved in ribosome and COVID-19 disease that may be potential targets for prognosis and novel therapeutic intervention in DLBCL.", "claims": [{"id": "claim-method", "statement": "We conducted gene co-expression analysis on the processed GSE12453 data using the weighted correlation network analysis (WGCNA) (Langfelder & Horvath, 2008; Langfelder & Horvath, 2012) in R (Team, 2019).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34760386", "locator": "sections[10] \"Co-expression network construction and identification of modules related to DLBCL\" paragraph 2", "quote": "We conducted gene co-expression analysis on the processed GSE12453 data using the weighted correlation network analysis (WGCNA) (Langfelder & Horvath, 2008; Langfelder & Horvath, 2012) in R (Team, 2019)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34760386", "locator": "sections[31] \"Data Availability\" paragraph 2", "quote": "The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34760386", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes."}, {"asset": "source:pmid:34760386", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We identified 46 differentially co-expressed hub genes in the GSE12453 dataset."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Gene expression levels and survival analysis found 15 differentially co-expressed core hub 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:34760386"], "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:GSE12453"], "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:GSE12453"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34760386", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.12394", "sha256": "sha256:0de742bc9192b30af87a954cc5f6943f721692e18dac2e25006c609172e848a4", "bytes": 73967, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.12394", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8570165", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12453", "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=GSE12453", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12453", "version": null, "note": "The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM312811", "GSM312812", "GSM312813", "GSM312814", "GSM312815", "GSM312816", "GSM312817", "GSM312818", "GSM312819", "GSM312820", "GSM312821", "GSM312822", "GSM312823", "GSM312824", "GSM312825", "GSM312826", "GSM312839", "GSM312840", "GSM312841", "GSM312843", "GSM312844", "GSM312845", "GSM312846", "GSM312847", "GSM312848", "GSM312849", "GSM312851", "GSM312853", "GSM312854", "GSM312856", "GSM312857", "GSM312858", "GSM312859", "GSM312860", "GSM312861", "GSM312862", "GSM312863", "GSM312864", "GSM312865", "GSM312867", "GSM312868", "GSM312869", "GSM312870", "GSM312872", "GSM312874", "GSM312875", "GSM312876", "GSM312877", "GSM312879", "GSM312882", "GSM312883", "GSM312886", "GSM312887", "GSM312890", "GSM312893", "GSM312894", "GSM312895", "GSM312937", "GSM312938", "GSM312939", "GSM312940", "GSM312941", "GSM312942", "GSM312943", "GSM312944", "GSM312945", "GSM312946"], "sample_count": 67, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Origin and pathogenesis of lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE31312", "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=GSE31312", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31312", "version": null, "note": "The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM775979", "GSM775980", "GSM775981", "GSM775982", "GSM775983", "GSM775984", "GSM775985", "GSM775986", "GSM775987", "GSM775988", "GSM775989", "GSM775990", "GSM775991", "GSM775992", "GSM775993", "GSM775994", "GSM775995", "GSM775996", "GSM775997", "GSM775998", "GSM775999", "GSM776000", "GSM776001", "GSM776002", "GSM776003", "GSM776004", "GSM776005", "GSM776006", "GSM776007", "GSM776008", "GSM776009", "GSM776010", "GSM776011", "GSM776012", "GSM776013", "GSM776014", "GSM776015", "GSM776016", "GSM776017", "GSM776018", "GSM776019", "GSM776020", "GSM776021", "GSM776022", "GSM776023", "GSM776024", "GSM776025", "GSM776026", "GSM776027", "GSM776028", "GSM776029", "GSM776030", "GSM776031", "GSM776032", "GSM776033", "GSM776034", "GSM776035", "GSM776036", "GSM776037", "GSM776038", "GSM776039", "GSM776040", "GSM776041", "GSM776042", "GSM776043", "GSM776044", "GSM776045", "GSM776046", "GSM776047", "GSM776048", "GSM776049", "GSM776050", "GSM776051", "GSM776052", "GSM776053", "GSM776054", "GSM776055", "GSM776056", "GSM776057", "GSM776058", "GSM776059", "GSM776060", "GSM776061", "GSM776062", "GSM776063", "GSM776064", "GSM776065", "GSM776066", "GSM776067", "GSM776068", "GSM776069", "GSM776070", "GSM776071", "GSM776072", "GSM776073", "GSM776074", "GSM776075", "GSM776076", "GSM776077", "GSM776078", "GSM776079", "GSM776080", "GSM776081", "GSM776082", "GSM776083", "GSM776084", "GSM776085", "GSM776086", "GSM776087", "GSM776088", "GSM776089", "GSM776090", "GSM776091", "GSM776092", "GSM776093", "GSM776094", "GSM776095", "GSM776096", "GSM776097", "GSM776098", "GSM776099", "GSM776100", "GSM776101", "GSM776102", "GSM776103", "GSM776104", "GSM776105", "GSM776106", "GSM776107", "GSM776108", "GSM776109", "GSM776110", "GSM776111", "GSM776112", "GSM776113", "GSM776114", "GSM776115", "GSM776116", "GSM776117", "GSM776118", "GSM776119", "GSM776120", "GSM776121", "GSM776122", "GSM776123", "GSM776124", "GSM776125", "GSM776126", "GSM776127", "GSM776128", "GSM776129", "GSM776130", "GSM776131", "GSM776132", "GSM776133", "GSM776134", "GSM776135", "GSM776136", "GSM776137", "GSM776138", "GSM776139", "GSM776140", "GSM776141", "GSM776142", "GSM776143", "GSM776144", "GSM776145", "GSM776146", "GSM776147", "GSM776148", "GSM776149", "GSM776150", "GSM776151", "GSM776152", "GSM776153", "GSM776154", "GSM776155", "GSM776156", "GSM776157", "GSM776158", "GSM776159", "GSM776160", "GSM776161", "GSM776162", "GSM776163", "GSM776164", "GSM776165", "GSM776166", "GSM776167", "GSM776168", "GSM776169", "GSM776170", "GSM776171", "GSM776172", "GSM776173", "GSM776174", "GSM776175", "GSM776176", "GSM776177", "GSM776178", "GSM776179", "GSM776180", "GSM776181", "GSM776182", "GSM776183", "GSM776184", "GSM776185", "GSM776186", "GSM776187", "GSM776188", "GSM776189", "GSM776190", "GSM776191", "GSM776192", "GSM776193", "GSM776194", "GSM776195", "GSM776196", "GSM776197", "GSM776198", "GSM776199", "GSM776200", "GSM776201", "GSM776202", "GSM776203", "GSM776204", "GSM776205", "GSM776206", "GSM776207", "GSM776208", "GSM776209", "GSM776210", "GSM776211", "GSM776212", "GSM776213", "GSM776214", "GSM776215", "GSM776216", "GSM776217", "GSM776218", "GSM776219", "GSM776220", "GSM776221", "GSM776222", "GSM776223", "GSM776224", "GSM776225", "GSM776226", "GSM776227", "GSM776228", "GSM776229", "GSM776230", "GSM776231", "GSM776232", "GSM776233", "GSM776234", "GSM776235", "GSM776236", "GSM776237", "GSM776238", "GSM776239", "GSM776240", "GSM776241", "GSM776242", "GSM776243", "GSM776244", "GSM776245", "GSM776246", "GSM776247", "GSM776248", "GSM776249", "GSM776250", "GSM776251", "GSM776252", "GSM776253", "GSM776254", "GSM776255", "GSM776256", "GSM776257", "GSM776258", "GSM776259", "GSM776260", "GSM776261", "GSM776262", "GSM776263", "GSM776264", "GSM776265", "GSM776266", "GSM776267", "GSM776268", "GSM776269", "GSM776270", "GSM776271", "GSM776272", "GSM776273", "GSM776274", "GSM776275", "GSM776276", "GSM776277", "GSM776278", "GSM776279", "GSM776280", "GSM776281", "GSM776282", "GSM776283", "GSM776284", "GSM776285", "GSM776286", "GSM776287", "GSM776288", "GSM776289", "GSM776290", "GSM776291", "GSM776292", "GSM776293", "GSM776294", "GSM776295", "GSM776296", "GSM776297", "GSM776298", "GSM776299", "GSM776300", "GSM776301", "GSM776302", "GSM776303", "GSM776304", "GSM776305", "GSM776306", "GSM776307", "GSM776308", "GSM776309", "GSM776310", "GSM776311", "GSM776312", "GSM776313", "GSM776314", "GSM776315", "GSM776316", "GSM776317", "GSM776318", "GSM776319", "GSM776320", "GSM776321", "GSM776322", "GSM776323", "GSM776324", "GSM776325", "GSM776326", "GSM776327", "GSM776328", "GSM776329", "GSM776330", "GSM776331", "GSM776332", "GSM776333", "GSM776334", "GSM776335", "GSM776336", "GSM776337", "GSM776338", "GSM776339", "GSM776340", "GSM776341", "GSM776342", "GSM776343", "GSM776344", "GSM776345", "GSM776346", 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Rituximab-CHOP Consortium Program Study", "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:GSE12453 not downloaded", "asset:data:geo:GSE12453 licence not read", "asset:data:geo:GSE31312 not downloaded", "asset:data:geo:GSE31312 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-3", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-4", "family": null, "specific": null, "label": "Weighted gene co-expression network analysis (WGCNA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We conducted gene co-expression analysis on the processed GSE12453 data using the weighted correlation network analysis (WGCNA) (Langfelder & Horvath, 2008; Langfelder & Horvath, 2012) in R (Team, 2019)."}}], "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": ["hierarchical_cluster"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: hierarchical."}, "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": ["GSE12453", "GSE31312"], "resolved_accessions": ["GSE12453", "GSE31312"], "statements": ["The following information was supplied regarding data availability:Previously reported expression datasets were used in this study and are available at NCBI-GEO: Dataset for differentially co-expressed genes identification: GSE12453.Dataset for survival and prognostic verification: GSE31312.The other databases used:Verification of hub gene expression levels and core hub gene expression levels in other tumors; GEPIA2 database: http://gepia.cancer-pku.cn/detail.php?gene=&clicktag=expdiy [Filters used: Expression DIY; Gene (names of the various hub genes); Datasets Selection (Cancer name, e.g., DLBC); Plot]. A full list of the hub genes and cancer names is available in the Supplemental File.Core hub gene expression levels in other tumors; Oncomine database: https://www.oncomine.org/resource/main.html (Filters used: Differential Analysis and Gene Summary. Search terms were the names of the various core hub genes).Protein expression levels by immunohistochemistry (IHC): The human protein atlas database; https://www.proteinatlas.org/ [(A) Search terms for cases: The Pathology Atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Pathology; Cancer: Lymphoma. (B) Search terms for normal tissues: Tissue atlas; names of the core hub genes (RPS21, MRPS28, RPL31, and RPL30); Tissues: lymph node]."], "basis": "The paper names GSE12453, GSE31312 in National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["hierarchical_cluster"], "assets": ["source:pmid:34760386", "data:geo:GSE12453"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12453"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:06:45Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 21422, "completion_tokens": 2360, "cached_tokens": 264}}, "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:34760386", "type": "paper", "label": "pmid:34760386"}, {"id": "source:pmid:34760386", "type": "manuscript", "label": "PMID 34760386 full text"}, {"id": "data:geo:GSE12453", "type": "dataset", "label": "GEO GSE12453"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34760386", "type": "paper", "label": "pmid:34760386"}, {"id": "source:pmid:34760386", "type": "manuscript", "label": "PMID 34760386 full text"}, {"id": "data:geo:GSE12453", "type": "dataset", "label": "GEO GSE12453"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34760386", "type": "extraction", "used": ["source:pmid:34760386"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12453", "type": "accession_resolution", "used": ["data:geo:GSE12453"], "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:34760386", "parent_hash": "sha256:a2d816ab7705be15352e3d4920c1d249983eedd037c0f33e55a917432465bc90", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE12453 licence not read", "asset:data:geo:GSE12453 not downloaded", "asset:data:geo:GSE31312 licence not read", "asset:data:geo:GSE31312 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rom non-tumor control cases (Fig. S6). Also, immunohistochemistry data from the human protein atlas (HPA) data", "plemental Information 7Immunohistochemistry (IHC) showing lymph node expression patterns of 4", "some selected tumor tissues. Q: quantity of IHC score; DLBCL: NHL high grade; LG: NHL-low gr"], "order_basis": "paper_text_order:5938", "id": "assay:1"}, {"role": "analysis", "definition_id": "clustering", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["hierarchical_cluster"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["hierarchical clustering"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}