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pmid:36438734

Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs.

Yinjiang Zhang · Yashuo Zhang · Rongfei Yao · Xu He · Linyi Zhao · Xiangyu Zuo · Binan Lu · Zongran Pang

Frontiers in nutrition · 2022 doi:10.3389/fnut.2022.1010918

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:36438734
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2026-11-01T19:00:54Z
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2026-11-01T22:50:41Z
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paper object · 10 fields
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title
Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs.
doi
10.3389/fnut.2022.1010918
pmid
36438734
authors array · 8 items
[0]
Yinjiang Zhang
[1]
Yashuo Zhang
[2]
Rongfei Yao
[3]
Xu He
[4]
Linyi Zhao
[5]
Xiangyu Zuo
[6]
Binan Lu
[7]
Zongran Pang
journal
Frontiers in nutrition
year
2022
abstract
Background: Iron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS. Materials and methods: GSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294. Results: Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets. Conclusion: Our findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.
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Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5).
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sections[7] "Identification of ferroptosis-related differentially expressed genes and functional analysis" paragraph 2
quote
Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5).
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
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Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls.
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Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls.
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Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls.
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Gene expression analysis of peripheral whole blood RNA following ischemic stroke
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Gene Expression Profiling of Ischemic Stroke at 0-24 hours and 24-48 hours after known onset of symptoms
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title
Gene Expression Following Cardioembolic Stroke
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Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5).
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Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36438734", "kind": "science-record", "revision": 4, "content_hash": "sha256:75be770afffc25d4260dc6848af1e495bd4ebd4cf7b5d83934e25a4fde370589", "created_at": "2026-11-01T19:00:54Z", "updated_at": "2026-11-01T22:50:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs.", "doi": "10.3389/fnut.2022.1010918", "pmid": "36438734", "authors": ["Yinjiang Zhang", "Yashuo Zhang", "Rongfei Yao", "Xu He", "Linyi Zhao", "Xiangyu Zuo", "Binan Lu", "Zongran Pang"], "journal": "Frontiers in nutrition", "year": 2022, "abstract": "Background: Iron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS.\nMaterials and methods: GSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294.\nResults: Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets.\nConclusion: Our findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.", "claims": [{"id": "claim-method", "statement": "Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36438734", "locator": "sections[7] \"Identification of ferroptosis-related differentially expressed genes and functional analysis\" paragraph 2", "quote": "Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36438734", "locator": "sections[32] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36438734", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls.", "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:36438734"], "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:GSE16561"], "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:GSE16561"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36438734", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fnut.2022.1010918", "sha256": "sha256:89cffa9bbb20ea4d1c9226853fce844c47be09ca18316036db1fa98aaa778440", "bytes": 35377, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fnut.2022.1010918", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9686348", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE16561", "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=GSE16561", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE16561", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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licence not read", "asset:data:geo:GSE58294 not downloaded", "asset:data:geo:GSE58294 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5)."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": 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adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE16561", "GSE37587", "GSE58294"], "resolved_accessions": ["GSE16561", "GSE37587", "GSE58294"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material."], "basis": "The paper names GSE16561, GSE37587, GSE58294 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36438734", "data:geo:GSE16561"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE16561"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:17:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10400, "completion_tokens": 2010, "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:36438734", "type": "paper", "label": "pmid:36438734"}, {"id": "source:pmid:36438734", "type": "manuscript", "label": "PMID 36438734 full text"}, {"id": "data:geo:GSE16561", "type": "dataset", "label": "GEO GSE16561"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36438734", "type": "paper", "label": "pmid:36438734"}, {"id": "source:pmid:36438734", "type": "manuscript", "label": "PMID 36438734 full text"}, {"id": "data:geo:GSE16561", "type": "dataset", "label": "GEO GSE16561"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36438734", "type": "extraction", "used": ["source:pmid:36438734"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE16561", "type": "accession_resolution", "used": ["data:geo:GSE16561"], "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:36438734", "parent_hash": "sha256:58845013c0bb0765be7073e74878167e4dded77f49569c87d3fbf43201611c6a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE16561 licence not read", "asset:data:geo:GSE16561 not downloaded", "asset:data:geo:GSE37587 licence not read", "asset:data:geo:GSE37587 not downloaded", "asset:data:geo:GSE58294 licence not read", "asset:data:geo:GSE58294 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Limma4 (18) was used to identify DEGs between IS and normal samples in the GSE16561 (adjustment p < 0.05 and | log2FC| > 0.5)."], "order_basis": "analysis_only", "id": "assay:1"}]}