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pmid:30665415
miRNAs and target genes in the blood as biomarkers for the early diagnosis of Parkinson's disease.
Xiaoting Liu · Jinhu Chen · Tianyuan Guan · Hui Yao · Wenpei Zhang · Zhenlong Guan · Yanqin Wang
BMC systems biology · 2019 doi:10.1186/s12918-019-0680-4
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Experiment
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Analysis
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Complete file
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The aim of this study is to construct a molecular network to find molecules that play important roles in the progression of PD with the goal of using them diagnostically and for early intervention.\nRESULTS: We downloaded two gene expression profiles (GSE54536 and GSE100054) from the Expression Omnibus (GEO) database to analyze possible markers. The Genes were analyzed with GEO2R. There were 1790 and 967 differentially expressed genes (DEGs) in GSE54536 and GSE100054 respectively. A total of 125 genes co-exist in the DEGs of the two data sets. KEGG pathway analysis showed that 125 DEGs were enriched in Aldosterone synthesis and secretion, Gap junctions, Platelet activation, Rap1 signaling pathway, and Estrogen signaling pathway. There were 20 hub genes among 125 DEGs analyzed by PPI that involved in Platelet activation, Inflammatory response, Innate immune response, B cell receptor signaling, Stimulatory C-type lectin receptor signaling, Lipopolysaccharide response, Leukocyte migration, and Regulation of cell proliferation. Additionally, 42 differences in miRNAs were found in GSE100054. We constructed a miRNA-mRNA regulatory network depicting interactions between the predicted genes and the 125 DEGs. 34 miRNA-mRNA pairs were obtained. We found GNAQ and TMTC2 were the most important mRNAs in the network analyzed by Cytoscape APP centiscape, and their degrees in centiscape2.2 were all 10. has-miR-142 was the most important miRNA (the highest degree is 4 in centiscape2.2), which forms miRNA-mRNA pairs with GNAQ, TMTC2, BEND2, and KYNU.\nCONCLUSIONS: This study provides data of potential biomarkers and therapeutic targets for PD diagnosis and treatment. Among them, hsa-miR-142 is a critical miRNA in the PD network, and may be involved in PD progression by regulating GNAQ, TMTC2, BEND2, and KYNU.", "claims": [{"id": "claim-method", "statement": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) is an online analysis tool used to perform comparisons between groups of samples in a GEO dataset to identify DEGs or DEMs across experimental conditions.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30665415", "locator": "sections[4] \"Differentially expressed mRNAs and miRNAs selection\" paragraph 2", "quote": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) is an online analysis tool used to perform comparisons between groups of samples in a GEO dataset to identify DEGs or DEMs across experimental conditions."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in the current study download from: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100054; and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54536.\nAll data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30665415", "locator": "sections[16] \"Availability of data and materials\" paragraphs 1-3", "quote": "The datasets analyzed in the current study download from: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100054; and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54536.\nAll data generated or analyzed during this study are included in this published article."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:30665415"], "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:GSE100054"], "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:GSE100054"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30665415", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12918-019-0680-4", "sha256": "sha256:96f8caead49cd2c0f79accb1eeb5498edfbc7df4a6db733320b0bf79903665c7", "bytes": 30081, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12918-019-0680-4", "version": null, "note": "Full article fetched from PMC; 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and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54536.\nAll data generated or analyzed during this study are included in this published article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in the current study download from: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100054; and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54536.\nAll data generated or analyzed during this study are included in this published article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1318547", "GSM1318548", "GSM1318549", "GSM1318550", "GSM1318551", "GSM1318552", "GSM1318553", "GSM1318554", "GSM1318555", "GSM1318556"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Involvement of endocytosis and alternative splicing in the formation of the pathological process in Parkinson's Disease", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:30665415:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:45d16c52ca15ca16aa274ebe025bc37fe60ce20fd44a830ea5f326d5432d3460", "bytes": 620, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab1", "version": null, "note": "miRNAs/genes confirmed related to PD", "structure": {"pmcid": "PMC6341689", "section_index": 13, "section_title": "Discussion", "row_count": 6, "column_count": 4}, "table": {"label": "Table 1", "caption": "miRNAs/genes confirmed related to PD", "rows": [["miRNAs/genes", "Disease", "Variation tendency", "Reference"], ["CD79A", "PD", "down-regulated", "Kobo H [15],"], ["NLRP3", "PD (mice Rotenone Exposure)", "up-reglulated", "Martinez EM [16], Zhou Y [17]"], ["miR-142-3p", "PD(patients plasma)", "down-regulated", "Chen L [18]"], ["miR-15b-5p", "PD(MPP+ damaged SH-SY5Y cells)", "down-regulated", "Xie N [19, 20]"], ["miR-590-3p", "(MPP+)-treated MES23.5 and SH-SY5Y cells", "down-regulated", "Wang J [22]"]], "row_count": 6, "column_count": 4, "numeric_cells": 10, "header_rows": 1, "locator": "section[13]/table-wrap[1]#Tab1"}}], "gaps": ["asset:data:geo:GSE100054 not downloaded", "asset:data:geo:GSE100054 licence not read", "asset:data:geo:GSE54536 not downloaded", "asset:data:geo:GSE54536 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-2", "family": null, "specific": null, "label": "GEO2R differential-expression analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) is an online analysis tool used to perform comparisons between groups of samples in a GEO dataset to identify DEGs or DEMs across experimental conditions."}}], "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": ["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. 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