Identification and characterization of biomarkers associated with endoplasmic reticulum protein processing in cerebral ischemia-reperfusion injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38188159", "kind": "science-record", "revision": 3, "content_hash": "sha256:aa003c55e7ca45abf9b108aae3b1b8ca36bf6314c2943740a509f430c644bb27", "created_at": "2026-11-01T19:20:06Z", "updated_at": "2026-11-01T22:10:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and characterization of biomarkers associated with endoplasmic reticulum protein processing in cerebral ischemia-reperfusion injury.", "doi": "10.7717/peerj.16707", "pmid": "38188159", "authors": ["Liang-da Li", "Yue Zhou", "Shan-Fen Shi"], "journal": "PeerJ", "year": 2024, "abstract": "Background: Cerebral ischemia (CI), ranking as the second leading global cause of death, is frequently treated by reestablishing blood flow and oxygenation. Paradoxically, this reperfusion can intensify tissue damage, leading to CI-reperfusion injury. This research sought to uncover biomarkers pertaining to protein processing in the endoplasmic reticulum (PER) during CI-reperfusion injury.\nMethods: We utilized the Gene Expression Omnibus (GEO) dataset GSE163614 to discern differentially expressed genes (DEGs) and single out PER-related DEGs. The functions and pathways of these PER-related DEGs were identified via Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Core genes were pinpointed through protein-protein interaction (PPI) networks. Subsequent to this, genes with diagnostic relevance were distinguished using external validation datasets. A single-sample gene-set enrichment analysis (ssGSEA) was undertaken to pinpoint genes with strong associations to hypoxia and apoptosis, suggesting their potential roles as primary inducers of apoptosis in hypoxic conditions during ischemia-reperfusion injuries.\nResults: Our study demonstrated that PER-related genes, specifically ADCY5, CAMK2A, PLCB1, NTRK2, and DLG4, were markedly down-regulated in models, exhibiting a robust association with hypoxia and apoptosis.\nConclusion: The data indicates that ADCY5, CAMK2A, PLCB1, NTRK2, and DLG4 could be pivotal genes responsible for triggering apoptosis in hypoxic environments during CI-reperfusion injury.", "claims": [{"id": "claim-method", "statement": "A single-sample gene-set enrichment analysis (ssGSEA) was undertaken to pinpoint genes with strong associations to hypoxia and apoptosis, suggesting their potential roles as primary inducers of apoptosis in hypoxic conditions during ischemia-reperfusion injuries.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38188159", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "A single-sample gene-set enrichment analysis (ssGSEA) was undertaken to pinpoint genes with strong associations to hypoxia and apoptosis, suggesting their potential roles as primary inducers of apoptosis in hypoxic conditions during ischemia-reperfusion injuries."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38188159", "locator": "sections[29] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study demonstrated that PER-related genes, specifically ADCY5, CAMK2A, PLCB1, NTRK2, and DLG4, were markedly down-regulated in models, exhibiting a robust association with hypoxia and apoptosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38188159", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our study demonstrated that PER-related genes, specifically ADCY5, CAMK2A, PLCB1, NTRK2, and DLG4, were markedly down-regulated in models, exhibiting a robust association with hypoxia and apoptosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our study demonstrated that PER-related genes, specifically ADCY5, CAMK2A, PLCB1, NTRK2, and DLG4, were markedly down-regulated in models, exhibiting a robust association with hypoxia and apoptosis.", "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:38188159"], "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:GSE163614"], "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:GSE163614"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38188159", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.16707", "sha256": "sha256:4224f2bf94d0cf06a7b1f89661aac377c0e73bd6cd8617253d7913d388d494af", "bytes": 39640, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.16707", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10768662", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE163614", "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=GSE163614", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE163614", "version": null, "note": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4982793", "GSM4982794", "GSM4982795", "GSM4982796", "GSM4982797", "GSM4982798"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "25947", "taxon": "Rattus norvegicus", "title": "Gene expression profile in cerebral ischemia-reperfusion injury of rat model", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE78731", "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=GSE78731", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE78731", "version": null, "note": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2074816", "GSM2074817", "GSM2074818", "GSM2074819", "GSM2074820", "GSM2074821", "GSM2074822", "GSM2074823", "GSM2074824", "GSM2074825", "GSM2074826", "GSM2074827", "GSM2074828", "GSM2074829", "GSM2074830", "GSM2074831"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "15084", "taxon": "Rattus norvegicus", "title": "mRNA microarray in MCAo rat model with IV-hUMSC", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE97537", "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=GSE97537", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE97537", "version": null, "note": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2571735", "GSM2571736", "GSM2571737", "GSM2571738", "GSM2571739", "GSM2571740", "GSM2571741", "GSM2571742", "GSM2571743", "GSM2571744", "GSM2571745", "GSM2571746"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "1355", "taxon": "Rattus norvegicus", "title": "Expression data from MCAO or Sham operated rat brain [mRNA]", "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:GSE163614 not downloaded", "asset:data:geo:GSE163614 licence not read", "asset:data:geo:GSE78731 not downloaded", "asset:data:geo:GSE78731 licence not read", "asset:data:geo:GSE97537 not downloaded", "asset:data:geo:GSE97537 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": "protein-protein interaction"}}, {"id": "method-2", "family": null, "specific": null, "label": "single-sample gene-set enrichment analysis (ssGSEA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A single-sample gene-set enrichment analysis (ssGSEA) was undertaken to pinpoint genes with strong associations to hypoxia and apoptosis, suggesting their potential roles as primary inducers of apoptosis in hypoxic conditions during ischemia-reperfusion injuries."}}], "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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE163614", "GSE78731", "GSE97537"], "resolved_accessions": ["GSE163614", "GSE78731", "GSE97537"], "statements": ["The following information was supplied regarding data availability:\nThe raw data is available at figshare: Li, Liangda (2023). Raw data.zip. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22632745.v1."], "basis": "The paper names GSE163614, GSE78731, GSE97537 in Gene Expression Omnibus (GEO) within the NCBI 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:38188159", "data:geo:GSE163614"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE163614"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:04:29Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12733, "completion_tokens": 1912, "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:38188159", "type": "paper", "label": "pmid:38188159"}, {"id": "source:pmid:38188159", "type": "manuscript", "label": "PMID 38188159 full text"}, {"id": "data:geo:GSE163614", "type": "dataset", "label": "GEO GSE163614"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38188159", "type": "paper", "label": "pmid:38188159"}, {"id": "source:pmid:38188159", "type": "manuscript", "label": "PMID 38188159 full text"}, {"id": "data:geo:GSE163614", "type": "dataset", "label": "GEO GSE163614"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38188159", "type": "extraction", "used": ["source:pmid:38188159"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE163614", "type": "accession_resolution", "used": ["data:geo:GSE163614"], "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:38188159", "parent_hash": "sha256:ae50d485864d7b797c40d98323eaf0c8273d769eb12a539292f97e1c003fb3c9", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE163614 licence not read", "asset:data:geo:GSE163614 not downloaded", "asset:data:geo:GSE78731 licence not read", "asset:data:geo:GSE78731 not downloaded", "asset:data:geo:GSE97537 licence not read", "asset:data:geo:GSE97537 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["enes with strong associations to hypoxia and apoptosis, suggesting their potential roles as primary", "their potential roles as primary inducers of apoptosis in hypoxic conditions during ischemia-reperf", "biting a robust association with hypoxia and apoptosis. Conclusion: The data indicates that ADCY5,", "be pivotal genes responsible for triggering apoptosis in hypoxic environments during CI-reperfusio"], "order_basis": "paper_text_order:1132", "id": "assay:1"}, {"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": "consumes_earlier_output", "id": "assay:2"}]}