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pmid:35273684
Integrated analysis of differentially expressed genes and a ceRNA network to identify hub lncRNAs and potential drugs for multiple sclerosis.
Tianfeng Wang · Si Xu · Li Liu · Shuang Li · Huixue Zhang · Xiaoyu Lu · Xiaotong Kong · Danyang Li · Jianjian Wang · Lihua Wang
American journal of translational research · 2022
Paper
partial
Experiment
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Data
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Analysis
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Execution
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Complete file
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However, the precise molecular mechanisms underlying MS have yet to be fully elucidated. In this study, our aim was to provide novel insight into the pathogenesis of MS and provide a resource for identifying new biomarkers and therapeutics for MS.\nMETHODS: In this study, we analyzed the gene expression profiles (GSE21942) and miRNA expression profiles (GSE61741) of MS patient samples that were downloaded from the GEO database and identified differentially expressed mRNAs and miRNAs (DEmRNAs, DEmiRNAs). Next, we constructed a protein-protein interaction (PPI) network and a MS-specific ceRNA network (MCEN) by integrating expression profiles, interaction pairs of mRNA-miRNAs and lncRNA-miRNAs. Then, according to the modular structure of the PPI network, we identified hub DEmRNAs and generated a ceRNA subnetwork so that we could analyze the key lncRNAs that were associated with MS.\nRESULTS: We first identified 4 modules by constructing a PPI network using DEmRNAs. Functional enrichment analysis showed these modules were enriched in immune-related pathways. Then, we constructed the MCEN and the hub gene-associated ceRNA subnetwork using a comprehensive computational approach. We identified three key lncRNAs (LINC00649, TP73-AS1 and MALAT1) and further identified key lncRNA-mediated ceRNAs within the subnetwork. Finally, by analyzing LINC00649-miR-1275-CD20, we identified 6 drugs that may represent novel drugs for MS.\nCONCLUSION: Collectively, our results provide novel insight for the discovery of biomarkers and therapeutics for MS and provide a suitable foundation from which to design future investigations of the pathogenic mechanisms associated with MS.", "claims": [{"id": "claim-data-access", "statement": "In this study, we analyzed the gene expression profiles (GSE21942) and miRNA expression profiles (GSE61741) of MS patient samples that were downloaded from the GEO database and identified differentially expressed mRNAs and miRNAs (DEmRNAs, DEmiRNAs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35273684", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In this study, we analyzed the gene expression profiles (GSE21942) and miRNA expression profiles (GSE61741) of MS patient samples that were downloaded from the GEO database and identified differentially expressed mRNAs and miRNAs (DEmRNAs, DEmiRNAs)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified three key lncRNAs (LINC00649, TP73-AS1 and MALAT1) and further identified key lncRNA-mediated ceRNAs within the subnetwork.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35273684", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified three key lncRNAs (LINC00649, TP73-AS1 and MALAT1) and further identified key lncRNA-mediated ceRNAs within the subnetwork."}], "state": "complete"}], "gaps": ["doi"]}, "experiment": {"state": "complete", "objective": "We identified three key lncRNAs (LINC00649, TP73-AS1 and MALAT1) and further identified key lncRNA-mediated ceRNAs within the subnetwork.", "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:35273684"], "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:GSE21942"], "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:GSE21942"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35273684", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": null, "sha256": "sha256:8f33aad8f3b20c750968c2ded425bc4c3c5f9ca19ff3ff1e1a27015fbfc65bae", "bytes": 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"GSM1513182", "GSM1513183", "GSM1513184", "GSM1513185", "GSM1513186"], "sample_count": 1049, "group_sizes": null, "group_sizes_basis": null, "platform": "9040", "taxon": "Homo sapiens", "title": "miRNA Profiles in patients and controls", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE21942 not downloaded", "asset:data:geo:GSE21942 licence not read", "asset:data:geo:GSE61741 not downloaded", "asset:data:geo:GSE61741 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"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "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": ["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": 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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": ["GSE21942", "GSE61741"], "resolved_accessions": ["GSE21942", "GSE61741"], "statements": ["In this study, we analyzed the gene expression profiles (GSE21942) and miRNA expression profiles (GSE61741) of MS patient samples that were downloaded from the GEO database and identified differentially expressed mRNAs and miRNAs (DEmRNAs, DEmiRNAs)."], "basis": "The paper names GSE21942, GSE61741 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:35273684", "data:geo:GSE21942"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE21942"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:37:17Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 5, "usage": {"prompt_tokens": 2003, "completion_tokens": 789, "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:35273684", "type": "paper", "label": "pmid:35273684"}, {"id": "source:pmid:35273684", "type": "manuscript", "label": "PMID 35273684 full text"}, {"id": "data:geo:GSE21942", "type": "dataset", "label": "GEO GSE21942"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35273684", "type": "paper", "label": "pmid:35273684"}, {"id": "source:pmid:35273684", "type": "manuscript", "label": "PMID 35273684 full text"}, {"id": "data:geo:GSE21942", "type": "dataset", "label": "GEO GSE21942"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35273684", "type": "extraction", "used": ["source:pmid:35273684"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE21942", "type": "accession_resolution", "used": ["data:geo:GSE21942"], "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:35273684", "parent_hash": "sha256:c57419f1d56c83aa20c92424e67a6dac0e83ddad8d13e0b4eb39605ff975623f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE21942 licence not read", "asset:data:geo:GSE21942 not downloaded", "asset:data:geo:GSE61741 licence not read", "asset:data:geo:GSE61741 not downloaded", "doi", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "analysis_only", "id": "assay:1"}]}