Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31899762", "kind": "science-record", "revision": 7, "content_hash": "sha256:dc12b26569013304b181172443bf37270a6ef9418d5799495f9b1c040315bb52", "created_at": "2026-11-01T15:40:54Z", "updated_at": "2026-11-01T22:01:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans.", "doi": "10.1371/journal.pone.0227481", "pmid": "31899762", "authors": ["Yan Lv", "X Y He", "Dongguo Li", "Tao Liu", "G Q Wen", "Junfa Li"], "journal": "PloS one", "year": 2020, "abstract": "BACKGROUND: Ischemic Stroke (IS) is a major disease which greatly threatens human health. Recent studies showed sex-specific outcomes and mechanisms of cerebral ischemic stroke. This study aimed to identify the key changes of gene expression between male and female IS in humans.\nMETHODS: Gene expression dataset GSE22255, including peripheral blood samples, was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially Expressed Genes (DEGs) with a LogFC>1, and a P-value <0.05 were screened by BioConductor R package and grouped in female, male and overlap DEGs for further bioinformatic analysis. Gene Ontology (GO) functional annotation, Protein-Protein Interaction (PPI) network, \"Molecular Complex Detection\" (MCODE) modules, CytoNCA (cytoscape network centrality analysis) essential genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway interrelation analysis were performed.\nRESULTS: In a total of 54,665 genes, 185 (73 ups and 112 downs) DEGs in the female dataset, 461 DEGs (297 ups and 164 downs) in the male dataset, within which 118 DEGs overlapped (7 similar changes in female and male, 111 opposite changes in female and male) were obtained from the GSE22255 dataset. Female, male and overlapping DEGs enriched for similar cellular components and molecular function. Male DEGs enriched for divergent biological processes from female and overlapping DEGs. Sex-specific and overlapping DEGs were put into the PPI network. Overlapping genes such as IL6, presented opposite changes and were mainly involved in cytokine-cytokine receptor interactions, the TNF-signalling pathway, etc.\nCONCLUSION: The analysis of sex-specific DEGs from GEO human blood samples showed that not only specific but also opposite DEG alterations in the female and male stroke genome wide dataset. The results provided an overview of sex-specific mechanisms, which might provide insight into stroke and its biomarkers and lead to sex-specific prognosis and treatment strategies in future clinical practice.", "claims": [{"id": "claim-method", "statement": "Enrichment tests were based on the hypergeometric distribution [25].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31899762", "locator": "sections[6] \"2.3.1 Gene ontology and pathway enrichment analysis of DEGs\" paragraph 2", "quote": "Enrichment tests were based on the hypergeometric distribution [25]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that all supporting data are available within the article [and its online supplementary files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31899762", "locator": "sections[3] \"2.1. Microarray data\" paragraph 2", "quote": "The authors declare that all supporting data are available within the article [and its online supplementary files]."}], "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:31899762"], "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:GSE22255"], "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:GSE22255"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31899762", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0227481", "sha256": "sha256:2a5a4d7b7f9fe36448f24fa2569d404195c0fe75b70a4343f6f4e6065494d1b1", "bytes": 21449, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0227481", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6941802", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE22255", "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=GSE22255", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22255", "version": null, "note": "The authors declare that all supporting data are available within the article [and its online supplementary files].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that all supporting data are available within the article [and its online supplementary files].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM554014", "GSM554015", "GSM554016", "GSM554017", "GSM554018", "GSM554019", "GSM554020", "GSM554021", "GSM554022", "GSM554023", "GSM554024", "GSM554025", "GSM554026", "GSM554027", "GSM554028", "GSM554029", "GSM554030", "GSM554031", "GSM554032", "GSM554033", "GSM554034", "GSM554035", "GSM554036", "GSM554037", "GSM554038", "GSM554039", "GSM554040", "GSM554041", "GSM554042", "GSM554043", "GSM554044", "GSM554045", "GSM554046", "GSM554047", "GSM554048", "GSM554049", "GSM554050", "GSM554051", "GSM554052", "GSM554053"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Blood genomic expression profile for ischemic stroke (IS)", "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:31899762:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:dfca167b4e3a3607a99616e9195072a1b164074fcb191d581815416ae48d962c", "bytes": 198, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#pone.0227481.t001", "version": null, "note": "GO enrichment analysis in networks.", "structure": {"pmcid": "PMC6941802", "section_index": 12, "section_title": "3.2.1 GO and pathway enrichment analysis", "row_count": 0, "column_count": 0}, "table": {"label": "Table 1", "caption": "GO enrichment analysis in networks.", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[12]/table-wrap[1]#pone.0227481.t001"}}, {"id": "asset:table:pmid:31899762:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a555149cc4b770ed30b4a17df021461012565e484276edf8c6a9cd284c6bb6a9", "bytes": 195, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#pone.0227481.t002", "version": null, "note": "MCODE modules from PPI networks.", "structure": {"pmcid": "PMC6941802", "section_index": 13, "section_title": "3.2.2. PPI network and module screening", "row_count": 0, "column_count": 0}, "table": {"label": "Table 2", "caption": "MCODE modules from PPI networks.", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[13]/table-wrap[1]#pone.0227481.t002"}}, {"id": "asset:table:pmid:31899762:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6ff92057636097fce0b564c79f84caa852c01295e86c04861158acd8007c27d2", "bytes": 229, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#pone.0227481.t003", "version": null, "note": "Interrelation between overlapping DEGs and enriched KEGG pathways.", "structure": {"pmcid": "PMC6941802", "section_index": 14, "section_title": "3.2.3. KEGG pathway enrichment and interrelation analysis", "row_count": 0, "column_count": 0}, "table": {"label": "Table 3", "caption": "Interrelation between overlapping DEGs and enriched KEGG pathways.", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[14]/table-wrap[1]#pone.0227481.t003"}}], "gaps": ["asset:data:geo:GSE22255 not downloaded", "asset:data:geo:GSE22255 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": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-3", "family": "network_analysis", "specific": "centrality", "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": "centrality"}}, {"id": "method-4", "family": null, "specific": null, "label": "Hypergeometric distribution", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Enrichment tests were based on the hypergeometric distribution [25]."}}], "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": ["GSE22255"], "resolved_accessions": ["GSE22255"], "statements": ["The authors declare that all supporting data are available within the article [and its online supplementary files]."], "basis": "The paper names GSE22255 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": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:31899762", "data:geo:GSE22255", "asset:table:pmid:31899762:1", "asset:table:pmid:31899762:2", "asset:table:pmid:31899762:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE22255"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:17:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 16410, "completion_tokens": 1052, "cached_tokens": 776}}, "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:31899762", "type": "paper", "label": "pmid:31899762"}, {"id": "source:pmid:31899762", "type": "manuscript", "label": "PMID 31899762 full text"}, {"id": "data:geo:GSE22255", "type": "dataset", "label": "GEO GSE22255"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31899762", "type": "paper", "label": "pmid:31899762"}, {"id": "source:pmid:31899762", "type": "manuscript", "label": "PMID 31899762 full text"}, {"id": "data:geo:GSE22255", "type": "dataset", "label": "GEO GSE22255"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31899762", "type": "extraction", "used": ["source:pmid:31899762"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE22255", "type": "accession_resolution", "used": ["data:geo:GSE22255"], "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:31899762", "parent_hash": "sha256:f400e994b1e8a2e3085801979e4cc9a5b7bf3b1ac68b95d8f8a3727891ccb473", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE22255 licence not read", "asset:data:geo:GSE22255 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": ["PPI"], "order_basis": "analysis_only", "id": "assay:1"}]}