Identification of BTK as an immune-related biomarker for Hashimoto's thyroiditis by integrated bioinformatic analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40022006", "kind": "science-record", "revision": 4, "content_hash": "sha256:c9efed4dbf1062f0e376037667be926cdb263e1c734e8214b2190663e57b4f6c", "created_at": "2026-11-01T20:30:14Z", "updated_at": "2026-11-01T22:56:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of BTK as an immune-related biomarker for Hashimoto's thyroiditis by integrated bioinformatic analysis.", "doi": "10.1186/s12865-025-00691-x", "pmid": "40022006", "authors": ["Yingzhao Liu", "Zhangwei Zhu", "Qian Xu", "Juan Xu", "Jie Xing", "Shengjun Wang", "Huiyong Peng"], "journal": "BMC immunology", "year": 2025, "abstract": "BACKGROUND: Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders characterized by diffuse enlargement of the thyroid gland, lymphocyte infiltration, and thyroid-specific autoantibodies. Cellular and humoral immune disorders have been implicated in the development of HT. However, little is known regarding the role of immune-related molecules in HT. This study was aimed to identify key immune-related biomarkers in HT by using bioinformatic analysis.\nMETHOD: Integration of the sequencing data from HT and normal control (NC) in the GSA and GTEx databases yielded a dataset named NGS. The GSE138198 dataset from the GEO database was downloaded as a validation set. WGCNA analysis was performed to identify key modules associated with HT. Lasso regression analysis (LASSO) and random forest (RF) were performed to determine potential diagnostic biomarkers. The potential value was assessed by using receiver operating characteristic (ROC) curve analysis. CIBERSORT algorithm was used to evaluate the infiltration of immune cells in HT and NC samples. The transcript levels of verified genes from expanded samples were detected by quantitative real-time PCR.\nRESULTS: A total of 1,401 differentially expressed genes (DEGs) were identified in HT patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these DEGs were predominantly enriched in immune-related pathways. Furthermore, 192 immune-related genes were identified in HT through the intersection of WGCNA modules, DEGs, and the IRGs. Among them, two upregulated genes ((Bruton's tyrosine kinase, BTK) and CD19) showed the potential diagnostic value for HT by using machine learning. The ROC curve analysis revealed that BTK had a higher diagnostic value than CD19 across two datasets. Intriguingly, only BTK expression was upregulated in the peripheral blood mononuclear cells of HT patients, and was significantly positively correlated with the serum levels of thyroid autoantibodies. Further studies confirmed a significant positive correlation between BTK and increased proportions of plasma cells in HT patients.\nCONCLUSION: This study identified BTK was significantly increased in HT patients, which might be the involved in the pathogenesis of HT by regulating plasma cells and represented a potential immune-related biomarker of HT.", "claims": [{"id": "claim-method", "statement": "The differentially expressed HT-related genes in NGS were determined by using the ‘limma’ package according to the criteria log2 foldchange (FC) > 1 and adjusted p < 0.05 [16].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40022006", "locator": "sections[4] \"Identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "The differentially expressed HT-related genes in NGS were determined by using the ‘limma’ package according to the criteria log2 foldchange (FC) > 1 and adjusted p < 0.05 [16]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the GSA-Human database/HRA001684 (https://ngdc.cncb.ac.cn/gsa-human/browse/HRA001684), GTEx database/phs000424. vpn. pn (https://www.gtexportal.org/home/downloads/adult-gtex/bulk_tissue_expression), and GEO/GSE138198 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138198) repository. All the raw data and source code are available. The link: https://www.jianguoyun.com/p/DeJocHYQ3OLUCRj7p6gFIAA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40022006", "locator": "sections[29] \"notes\" paragraph 1", "quote": "The datasets generated and/or analysed during the current study are available in the GSA-Human database/HRA001684 (https://ngdc.cncb.ac.cn/gsa-human/browse/HRA001684), GTEx database/phs000424. vpn. pn (https://www.gtexportal.org/home/downloads/adult-gtex/bulk_tissue_expression), and GEO/GSE138198 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138198) repository. All the raw data and source code are available. The link: https://www.jianguoyun.com/p/DeJocHYQ3OLUCRj7p6gFIAA."}], "state": "complete"}, {"id": "claim-target-result", "statement": "BTK was significantly increased in HT patients, might be involved in the pathogenesis of HT by regulating plasma cells, and represents a potential immune-related biomarker of HT.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40022006", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study identified BTK was significantly increased in HT patients, which might be the involved in the pathogenesis of HT by regulating plasma cells and represented a potential immune-related biomarker of HT."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "BTK was significantly increased in HT patients, might be involved in the pathogenesis of HT by regulating plasma cells, and represents a potential immune-related biomarker of HT.", "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:40022006"], "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:GSE138198"], "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:GSE138198"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40022006", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12865-025-00691-x", "sha256": "sha256:ff22dc2a0a517228cc548d8dad1a04c8df505e009552438e18db1e251a367ad7", "bytes": 33028, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12865-025-00691-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11869739", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE138198", "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=GSE138198", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138198", "version": null, "note": "The datasets generated and/or analysed during the current study are available in the GSA-Human database/HRA001684 (https://ngdc.cncb.ac.cn/gsa-human/browse/HRA001684), GTEx database/phs000424. vpn. pn (https://www.gtexportal.org/home/downloads/adult-gtex/bulk_tissue_expression), and GEO/GSE138198 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138198) repository. All the raw data and source code are available. The link: https://www.jianguoyun.com/p/DeJocHYQ3OLUCRj7p6gFIAA.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analysed during the current study are available in the GSA-Human database/HRA001684 (https://ngdc.cncb.ac.cn/gsa-human/browse/HRA001684), GTEx database/phs000424. vpn. pn (https://www.gtexportal.org/home/downloads/adult-gtex/bulk_tissue_expression), and GEO/GSE138198 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138198) repository. All the raw data and source code are available. The link: https://www.jianguoyun.com/p/DeJocHYQ3OLUCRj7p6gFIAA.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4101749", "GSM4101750", "GSM4101751", "GSM4101752", "GSM4101753", "GSM4101754", "GSM4101755", "GSM4101756", "GSM4101757", "GSM4101758", "GSM4101759", "GSM4101760", "GSM4101761", "GSM4101762", "GSM4101763", "GSM4101764", "GSM4101765", "GSM4101766", "GSM4101767", "GSM4101768", "GSM4101769", "GSM4101770", "GSM4101771", "GSM4101772", "GSM4101773", "GSM4101774", "GSM4101775", "GSM4101776", "GSM4101777", "GSM4101778", "GSM4101779", "GSM4101780", "GSM4101781", "GSM4101782", "GSM4101783", "GSM4101784"], "sample_count": 36, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Differentially expression profiling in Hashimoto's thyroiditis (HT), papillary thyroid carcinoma (PTC) with HT in background, PTC without HT in background, micro PTC (mPTC), and three normal thyroid samples (TN).", "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:GSE138198 not downloaded", "asset:data:geo:GSE138198 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The differentially expressed HT-related genes in NGS were determined by using the ‘limma’ package according to the criteria log2 foldchange (FC) > 1 and adjusted p < 0.05 [16]."}}, {"id": "method-2", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "random forest"}}, {"id": "method-3", "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-4", "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": "GO enrichment"}}, {"id": "method-5", "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": 0.7, "band": "medium", "quote": "ROC curve"}}], "targets": [], "gaps": []}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40022006", "data:geo:GSE138198"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE138198"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:47:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9664, "completion_tokens": 1816, "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:40022006", "type": "paper", "label": "pmid:40022006"}, {"id": "source:pmid:40022006", "type": "manuscript", "label": "PMID 40022006 full text"}, {"id": "data:geo:GSE138198", "type": "dataset", "label": "GEO GSE138198"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40022006", "type": "paper", "label": "pmid:40022006"}, {"id": "source:pmid:40022006", "type": "manuscript", "label": "PMID 40022006 full text"}, {"id": "data:geo:GSE138198", "type": "dataset", "label": "GEO GSE138198"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40022006", "type": "extraction", "used": ["source:pmid:40022006"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE138198", "type": "accession_resolution", "used": ["data:geo:GSE138198"], "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:40022006", "parent_hash": "sha256:3d5d9a7eaaec34a5c004f499c5dc9f5a48739c5bfb760b56bf2157c58000d754", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE138198 licence not read", "asset:data:geo:GSE138198 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "amplicon_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["A and GTEx databases yielded a dataset named NGS. The GSE138198 dataset from the GEO database", "d ROC curve analysis for BTK and CD19 in the NGS dataset and GSE138198 dataset, respectively.", "espectively. The AUCs of BTK and CD19 in the NGS dataset were 0.98 and 0.99, respectively (Fi", "ificantly upregulated in HT patients in both NGS and GSE138198 datasets (Fig. 6E). These data"], "order_basis": "paper_text_order:678", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["panded samples were detected by quantitative real-time PCR. RESULTS: A total of 1,401 differentially ex"], "order_basis": "paper_text_order:1240", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The differentially expressed HT-related genes in NGS were determined by using the ‘limma’ package according to the criteria log2 foldchange (FC) > 1 and adjusted p < 0.05 [16]."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}