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pmid:40748556
Meta-Analysis of Gene Expression Reveals the Core Transcriptomic Profile of Lesional Scalp in Alopecia Areata.
Irene Rivera-Ruiz · Jesús Gay-Mimbrera · Pedro J Gómez-Arias · Macarena Aguilar-Luque · Miguel Juan-Cencerrado · Carmen Mochón-Jiménez · Esmeralda Parra-Peralbo · Beatriz Isla-Tejera · Francisco Gómez-García · Juan Ruano
Dermatology and therapy · 2025 doi:10.1007/s13555-025-01471-6
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Experiment
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Analysis
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Execution
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Complete file
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Current research yields varied lists of differentially expressed genes (DEGs). A meta-analytic approach is essential to consolidate these findings into a consistent tissue signature. This study aimed to perform a meta-analysis of gene expression datasets to establish a comprehensive molecular signature of AA lesional scalp.\nMETHODS: We conducted a meta-analysis of transcriptomic data from human studies on lesional skin gene expression in AA. Reanalyzing 132 samples (82 patients with AA and 50 controls) from five Gene Expression Omnibus (GEO) datasets (GSE68801, GSE45512, GSE80342, GSE58573, GSE74761), we employed an effect size approach within a random-effects model to identify unique and shared DEGs and enriched biological pathways. The protocol is registered in PROSPERO (CRD42024559847).\nRESULTS: The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies. Consistently expressed genes included CXCL9, CCL18, CXCL10, CD8A, and GZMB (FDR < 0.05). The analysis highlighted chemokines/receptors (CCL13, CCR1, XCL1) and markers of cytotoxic T lymphocytes (GZMA, GZMH, GZMK) and NK cells (NKG2A, NKG2D). Downregulated genes involved type I (KRT31-35, KRT38) and type II (KRT81-86) keratins and proteins crucial for hair follicle structure and function (PADI3, GPRC5D, DSG4, FGF18). Functional analysis showed enrichment in Th1, Th2, and Th17 pathways, particularly through JAK-STAT signaling (p < 0.01).\nCONCLUSION: This core transcriptome of AA lesions provides new insights into the disease's pathogenesis and identifies potential targets for treatment.", "claims": [{"id": "claim-method", "statement": "After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40748556", "locator": "sections[6] \"Meta-Analysis\" paragraph 2", "quote": "After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. 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Additional data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40748556", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies.", "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:40748556"], "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:GSE45512"], "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:GSE45512"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40748556", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s13555-025-01471-6", "sha256": "sha256:1d5492b14f4fc82d033d43b41eff78aa624942282813eb60f3a068866c3dd69a", "bytes": 39346, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s13555-025-01471-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12454715", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE45512", "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=GSE45512", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE45512", "version": null, "note": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. 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Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1414312", "GSM1414313", "GSM1414314", "GSM1414315", "GSM1414316", "GSM1414317", "GSM1414318"], "sample_count": 7, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "First ruxolitinib treatment of human alopecia areata patients", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE68801", "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=GSE68801", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68801", "version": null, "note": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. 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Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2124815", "GSM2124816", "GSM2124817", "GSM2124818", "GSM2124819", "GSM2124820", "GSM2124821", "GSM2124822", "GSM2124823", "GSM2124824", "GSM2124825", "GSM2124826", "GSM2124827", "GSM2124828", "GSM2124829", "GSM2124830", "GSM2124831", "GSM2124832", "GSM2124833", "GSM2124834", "GSM2124835", "GSM2124836", "GSM2124837", "GSM2124838", "GSM2124839", "GSM2124840", "GSM2124841", "GSM2124842", "GSM2124843", "GSM2124844", "GSM2124845"], "sample_count": 31, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Pilot open label clinical trial of oral ruxolitinib in patients with alopecia areata", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE45512 not downloaded", "asset:data:geo:GSE45512 licence not read", "asset:data:geo:GSE58573 not downloaded", "asset:data:geo:GSE58573 licence not read", "asset:data:geo:GSE68801 not downloaded", "asset:data:geo:GSE68801 licence not read", "asset:data:geo:GSE74761 not downloaded", "asset:data:geo:GSE74761 licence not read", "asset:data:geo:GSE80342 not downloaded", "asset:data:geo:GSE80342 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "meta_analysis", "specific": "random_effects", "label": "Meta-analysis / evidence synthesis", "dsl_operations": ["random_effects_pool"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["study_level_effect_estimates"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05."}}], "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": ["random_effects_pool"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_effects."}, "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": ["GSE68801", "GSE45512", "GSE80342", "GSE58573", "GSE74761"], "resolved_accessions": ["GSE68801", "GSE45512", "GSE80342", "GSE58573", "GSE74761"], "statements": ["The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE68801, GSE45512, GSE80342, GSE58573, GSE74761 in National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["random_effects_pool"], "assets": ["source:pmid:40748556", "data:geo:GSE45512"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE45512"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:58:17Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9897, "completion_tokens": 1844, "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:40748556", "type": "paper", "label": "pmid:40748556"}, {"id": "source:pmid:40748556", "type": "manuscript", "label": "PMID 40748556 full text"}, {"id": "data:geo:GSE45512", "type": "dataset", "label": "GEO GSE45512"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40748556", "type": "paper", "label": "pmid:40748556"}, {"id": "source:pmid:40748556", "type": "manuscript", "label": "PMID 40748556 full text"}, {"id": "data:geo:GSE45512", "type": "dataset", "label": "GEO GSE45512"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40748556", "type": "extraction", "used": ["source:pmid:40748556"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE45512", "type": "accession_resolution", "used": ["data:geo:GSE45512"], "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:40748556", "parent_hash": "sha256:2fed921adc6c2fdeaa0b49ca89bc033ff54cb343944aac610421a249e26a4f36", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE45512 licence not read", "asset:data:geo:GSE45512 not downloaded", "asset:data:geo:GSE58573 licence not read", "asset:data:geo:GSE58573 not downloaded", "asset:data:geo:GSE68801 licence not read", "asset:data:geo:GSE68801 not downloaded", "asset:data:geo:GSE74761 licence not read", "asset:data:geo:GSE74761 not downloaded", "asset:data:geo:GSE80342 licence not read", "asset:data:geo:GSE80342 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "meta_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["random_effects_pool"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05."], "order_basis": "analysis_only", "id": "assay:1"}]}