Unsupervised Hierarchical Clustering Identifies Immune Gene Subtypes in Gastric Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34248641", "kind": "science-record", "revision": 7, "content_hash": "sha256:272ee1fde2e9ff83c2de740c6a3c292032c57a06a05ed10ea2954ec684b5b6f8", "created_at": "2026-11-01T15:41:42Z", "updated_at": "2026-11-01T22:04:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unsupervised Hierarchical Clustering Identifies Immune Gene Subtypes in Gastric Cancer.", "doi": "10.3389/fphar.2021.692454", "pmid": "34248641", "authors": ["Jing Cao", "Jiao Gong", "Xinhua Li", "Zhaoxia Hu", "Yingjun Xu", "Hong Shi", "Danyang Li", "Guangjian Liu", "Yusheng Jie", "Bo Hu", "Yutian Chong"], "journal": "Frontiers in pharmacology", "year": 2021, "abstract": "Objectives: The pathogenesis of heterogeneity in gastric cancer (GC) is not clear and presents as a significant obstacle in providing effective drug treatment. We aimed to identify subtypes of GC and explore the underlying pathogenesis. Methods: We collected two microarray datasets from GEO (GSE84433 and GSE84426), performed an unsupervised cluster analysis based on gene expression patterns, and identified related immune and stromal cells. Then, we explored the possible molecular mechanisms of each subtype by functional enrichment analysis and identified related hub genes. Results: First, we identified three clusters of GC by unsupervised hierarchical clustering, with average silhouette width of 0.96, and also identified their related representative genes and immune cells. We validated our findings using dataset GSE84426. Subtypes associated with the highest mortality (subtype 2 in the training group and subtype C in the validation group) showed high expression of SPARC, COL3A1, and CCN. Both subtypes also showed high infiltration of fibroblasts, endothelial cells, hematopoietic stem cells, and a high stromal score. Furthermore, subtypes with the best prognosis (subtype 3 in the training group and subtype A in the validation group) showed high expression of FGL2, DLGAP1-AS5, and so on. Both subtypes also showed high infiltration of CD4+ T cells, CD8+ T cells, NK cells, pDC, macrophages, and CD4+ T effector memory cells. Conclusion: We found that GC can be classified into three subtypes based on gene expression patterns and cell composition. Findings of this study help us better understand the tumor microenvironment and immune milieu associated with heterogeneity in GC and provide practical information to guide personalized treatment.", "claims": [{"id": "claim-method", "statement": "Then, the clustering method, consensus nonnegative matrix factorization (NMF), was used to identify different subtypes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34248641", "locator": "sections[4] \"Unsupervised Cluster Analysis\" paragraph 2", "quote": "Then, the clustering method, consensus nonnegative matrix factorization (NMF), was used to identify different subtypes."}], "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:34248641", "locator": "sections[17] \"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"}], "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:34248641"], "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:GSE84426"], "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:GSE84426"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34248641", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2021.692454", "sha256": "sha256:275685e1cb8dbe3a303e026be7ab83ec77649c46d54194f69b96923d9e82968e", "bytes": 33894, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2021.692454", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8264374", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE84426", "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=GSE84426", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE84426", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:34248641", "data:geo:GSE84426", "asset:table:pmid:34248641:1", "asset:table:pmid:34248641:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE84426"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:00Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 26544, "completion_tokens": 1362, "cached_tokens": 784}}, "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:34248641", "type": "paper", "label": "pmid:34248641"}, {"id": "source:pmid:34248641", "type": "manuscript", "label": "PMID 34248641 full text"}, {"id": "data:geo:GSE84426", "type": "dataset", "label": "GEO GSE84426"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34248641", "type": "paper", "label": "pmid:34248641"}, {"id": "source:pmid:34248641", "type": "manuscript", "label": "PMID 34248641 full text"}, {"id": "data:geo:GSE84426", "type": "dataset", "label": "GEO GSE84426"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34248641", "type": "extraction", "used": ["source:pmid:34248641"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE84426", "type": "accession_resolution", "used": ["data:geo:GSE84426"], "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:34248641", "parent_hash": "sha256:fe40b1c9358f10f125b8a53db8b50fceea3f9b85531c47abbdad90c73d11e2a5", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE84426 licence not read", "asset:data:geo:GSE84426 not downloaded", "asset:data:geo:GSE84433 licence not read", "asset:data:geo:GSE84433 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ying pathogenesis. Methods: We collected two microarray datasets from GEO (GSE84433 and GSE84426), p", "Method Patients and Gene Expression Microarray Data Acquisition The National Center for Bio", "roughput gene expression sequencing data and microarray data. Gene expression profile of GSE84433 ba", "mune Cell Analysis of Validation Set Another microarray dataset (GSE84426) consisting of 76 cases of"], "order_basis": "paper_text_order:306", "id": "assay:1"}, {"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": 0.8, "evidence": ["limma"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}