CD8+T Cell-Related Gene Biomarkers in Macular Edema of Diabetic Retinopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35937822", "kind": "science-record", "revision": 4, "content_hash": "sha256:99c69a687d854ac4adefcd79ec0f2286a6a0eed63d5e773bc2c9ae10a760d9d3", "created_at": "2026-11-01T18:15:02Z", "updated_at": "2026-11-01T22:07:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CD8+T Cell-Related Gene Biomarkers in Macular Edema of Diabetic Retinopathy.", "doi": "10.3389/fendo.2022.907396", "pmid": "35937822", "authors": ["Jing Huang", "Qiong Zhou"], "journal": "Frontiers in endocrinology", "year": 2022, "abstract": "Background: CD8+T lymphocytes have a strong pro-inflammatory effect in all parts of the tissue, and some studies have demonstrated that its concentration in the vitreous increased significantly, suggesting that CD8+T cells play a pivotal role in the inflammatory response of diabetic retinopathy (DR). However, the infiltration of CD8+T cells in the DR retina, especially in diabetic macular edema (DME), and its related genes are still unclear.\nMethods: Download the GSE16036 dataset from the Gene Expression Omnibus (GEO) database. The ImmuCellAI program was performed to evaluate the abundance of 24 immune cells including CD8+T cells. The CD8+T cell-related genes (DECD8+TRGs) between non-proliferative diabetic retinopathy (NPDR) and DME were detected via difference analysis and correlation analysis. Enrichment analysis and protein-protein interaction (PPI) network mapping were implemented to explore the potential function of DECD8+TRGs. Lasso regression, support vector machine recursive feature elimination (SVM-RFE), CytoHubba plug-in and MCODE plug-in in Cytoscape software, and Weighted Gene Co-Expression Network Analysis (WGCNA) were performed to comprehensively analyze and obtain Hub DECD8+TRGs. Hub DECD8+TRGs expression patterns were further validated in other two DR-related independent datasets. The CD8+TRG score was defined as the genetic characterization of Hub DECD8+TRGs using the GSVA sample scoring method, which can be administered to distinguish early and advanced diabetic nephropathy (DN) as well as normal and DN. Finally, the transcription level of DECD8+TRGs in DR model mouse were verified by quantitative real-time PCR (qPCR).\nResults: A total of 371 DECD8+TRGs were identified, of which 294 genes were positively correlated and only 77 genes were negatively correlated. Eight genes (IKZF1, PTPRC, ITGB2, ITGAX, TLR7, LYN, CD74, SPI1) were recognized as Hub DECD8+TRGs. DR and DN, which have strong clinical correlation, have been proved to be associated with CD8+T cell-related hub genes by multiple independent data sets. Hub DECD8+TRGs can not only distinguish PDR from normal and DN from normal, but also play a role in the early and progressive stages of the two diseases (NPDR vs DME, Early DN vs Advanced DN). The qPCR transcription level and trend of Hub DECD8+TRGs in DR mouse model was basically the same as that in human transcriptome.\nConclusion: This study not only increases our understanding of the molecular mechanism of CD8+T cells in the progression of DME, but also expands people's cognitive vision of the molecular mechanism of crosstalk of CD8+T cells in the eyes and kidneys of patients with diabetes.", "claims": [{"id": "claim-method", "statement": "Pearson correlation analysis of statistically significant DEGs expression and CD8+T cell abundance was performed to determine DECD8+TRGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35937822", "locator": "sections[5] \"Identification of DECD8+TRGs\" paragraph 2", "quote": "Pearson correlation analysis of statistically significant DEGs expression and CD8+T cell abundance was performed to determine DECD8+TRGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35937822", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Eight genes (IKZF1, PTPRC, ITGB2, ITGAX, TLR7, LYN, CD74, SPI1) were recognized as Hub DECD8+TRGs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35937822", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Eight genes (IKZF1, PTPRC, ITGB2, ITGAX, TLR7, LYN, CD74, SPI1) were recognized as Hub DECD8+TRGs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Eight genes (IKZF1, PTPRC, ITGB2, ITGAX, TLR7, LYN, CD74, SPI1) were recognized as Hub DECD8+TRGs.", "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:35937822"], "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:GSE142025"], "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:GSE142025"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35937822", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2022.907396", "sha256": "sha256:181ba6c9b237309632555d39122881cac12bfb350685544b2fc806324eb127b1", "bytes": 63019, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2022.907396", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9355330", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE142025", "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=GSE142025", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE142025", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE160306", "GSE94019", "GSE60436", "GSE142025", "GSE30528", "GSE96804"], "resolved_accessions": ["GSE160306", "GSE94019", "GSE60436", "GSE142025", "GSE30528", "GSE96804"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."], "basis": "The paper names GSE160306, GSE94019, GSE60436, GSE142025, GSE30528, GSE96804 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:35937822", "data:geo:GSE142025"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE142025"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:59:13Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15779, "completion_tokens": 2488, "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:35937822", "type": "paper", "label": "pmid:35937822"}, {"id": "source:pmid:35937822", "type": "manuscript", "label": "PMID 35937822 full text"}, {"id": "data:geo:GSE142025", "type": "dataset", "label": "GEO GSE142025"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35937822", "type": "paper", "label": "pmid:35937822"}, {"id": "source:pmid:35937822", "type": "manuscript", "label": "PMID 35937822 full text"}, {"id": "data:geo:GSE142025", "type": "dataset", "label": "GEO GSE142025"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35937822", "type": "extraction", "used": ["source:pmid:35937822"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE142025", "type": "accession_resolution", "used": ["data:geo:GSE142025"], "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:35937822", "parent_hash": "sha256:23570a84730f382ea5020bd33f3629f227cf2b2ec3053451162dbfcc9eae533f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE142025 licence not read", "asset:data:geo:GSE142025 not downloaded", "asset:data:geo:GSE160306 licence not read", "asset:data:geo:GSE160306 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE30528 not downloaded", "asset:data:geo:GSE60436 licence not read", "asset:data:geo:GSE60436 not downloaded", "asset:data:geo:GSE94019 licence not read", "asset:data:geo:GSE94019 not downloaded", "asset:data:geo:GSE96804 licence not read", "asset:data:geo:GSE96804 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tion level and trend of Hub DECD8+TRGs in DR mouse model was basically the same as that in human tran", "ranscription level of DECD8+TRGs in DR model mouse were verified by quantitative real-time PCR", "tion level and trend of Hub DECD8+TRGs in DR mouse model was basically the same as that in huma"], "order_basis": "paper_text_order:1639", "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": 0.99, "evidence": ["were verified by quantitative real-time PCR (qPCR). Results: A total of 371 DECD8+TRGs were id", "(NPDR vs DME, Early DN vs Advanced DN). The qPCR transcription level and trend of Hub DECD8+T", "DR model mouse were verified by quantitative real-time PCR (qPCR). Results: A total of 371 DECD8+TRGs w"], "order_basis": "paper_text_order:1675", "id": "assay:2"}, {"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": ["odel was basically the same as that in human transcriptome. Conclusion: This study not only increases o", "enrichment results of microarray and RNA-seq transcriptome. As an analytical method, it is usually used", "s, including CD8+T cells, was estimated from RNA-seq digital gene expression matrix data by the I", "ene set enrichment results of microarray and RNA-seq transcriptome. As an analytical method, it i"], "order_basis": "paper_text_order:2402", "id": "assay:3"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["evaluate the gene set enrichment results of microarray and RNA-seq transcriptome. As an analytical"], "order_basis": "paper_text_order:7911", "id": "assay:4"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Pearson correlation analysis of statistically significant DEGs expression and CD8+T cell abundance was performed to determine DECD8+TRGs."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}