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pmid:36776400
Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis.
Yucheng Wang · Xiaoli Lin · Cuili Wang · Xinyu Liu · Xiaoying Wu · Yingying Qiu · Ying Chen · Qin Zhou · Haige Zhao · Jianghua Chen · Hongfeng Huang
Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.1076546
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Experiment
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Complete file
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It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.\nMethods: Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway-T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.\nResults: A total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.\nConclusions: Our study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.", "claims": [{"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36776400", "locator": "sections[17] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The expression levels of CD4+PD1+CD57- T cells and CD8+PD1+CD57- T cells in the AR samples were significantly lower than both the STA samples and the healthy control ( Figures 4A, B , 5A, B , P<0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "The expression levels of CD4+PD1+CD57- T cells and CD8+PD1+CD57- T cells in the AR samples were significantly lower than both the STA samples and the healthy control ( Figures 4A, B , 5A, B , P<0.05)."}, "evidence": [{"asset": "source:pmid:36776400", "locator": "sections[15] \"Association of hub gene expression with acute rejection\" paragraph 2", "quote": "The expression levels of CD4+PD1+CD57- T cells and CD8+PD1+CD57- T cells in the AR samples were significantly lower than both the STA samples and the healthy control ( Figures 4A, B , 5A, B , P<0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The expression levels of CD4+PD1+CD57- T cells and CD8+PD1+CD57- T cells in the AR samples were significantly lower than both the STA samples and the healthy control ( Figures 4A, B , 5A, B , P<0.05).", "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:36776400"], "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. 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"Homo sapiens", "title": "Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE1563 not downloaded", "asset:data:geo:GSE1563 licence not read", "asset:data:geo:GSE174020 not downloaded", "asset:data:geo:GSE174020 licence not read", "asset:data:geo:GSE25902 not downloaded", "asset:data:geo:GSE25902 licence not read", "asset:data:geo:GSE36059 not downloaded", "asset:data:geo:GSE36059 licence not read", "asset:data:geo:GSE98320 not downloaded", "asset:data:geo:GSE98320 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], 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A run that reproduces the effect is judged against this threshold."}], "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE1563", "GSE25902", "GSE36059", "GSE98320", "GSE174020"], "resolved_accessions": ["GSE1563", "GSE25902", "GSE36059", "GSE98320", "GSE174020"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."], "basis": "The paper names GSE1563, GSE25902, GSE36059, GSE98320, GSE174020 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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