Analysis of gene expression profiles in Alzheimer's disease patients with different lifespan: A bioinformatics study focusing on the disease heterogeneity.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36909942", "kind": "science-record", "revision": 4, "content_hash": "sha256:912bc076655ee241408f5d2c0013e1991ecc2b9588372e30f38a0212bbfd08d9", "created_at": "2026-11-01T19:01:32Z", "updated_at": "2026-11-01T22:51:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of gene expression profiles in Alzheimer's disease patients with different lifespan: A bioinformatics study focusing on the disease heterogeneity.", "doi": "10.3389/fnagi.2023.1072184", "pmid": "36909942", "authors": ["Ji Zhang", "Xiaojia Li", "Jun Xiao", "Yang Xiang", "Fang Ye"], "journal": "Frontiers in aging neuroscience", "year": 2023, "abstract": "Objective: Alzheimer's disease (AD) as the most frequent neurodegenerative disease is featured by gradual decline of cognition and social function in the elderly. However, there have been few studies focusing on AD heterogeneity which exists both genetically and clinically, leading to the difficulties of AD researches. As one major kind of clinical heterogeneity, the lifespan of AD patients varies significantly. Aiming to investigate the potential driving factors, the current research identified the differentially expressed genes (DEGs) between longer-lived AD patients and shorter-lived ones via bioinformatics analyses.\nMethods: Qualified datasets of gene expression profiles were identified in National Center of Biotechnology Information Gene Expression Omnibus (NCBI-GEO). The data of the temporal lobes of patients above 60 years old were used. Two groups were divided according to the lifespan: the group ≥85 years old and the group <85 years old. Then GEO2R online software and R package of Robust Rank Aggregation (RRA) were used to screen DEGs. Bioinformatic tools were adopted to identify possible pathways and construct protein-protein interaction network.\nResult: Sixty-seven AD cases from four qualified datasets (GSE28146, GSE5281, GSE48350, and GSE36980) were included in this study. 740 DEGs were identified with 361 upregulated and 379 downregulated when compared longer-lived AD patients with shorter-lived ones. These DEGs were primarily involved in the pathways directly or indirectly associated with the regulation of neuroinflammation and cancer pathogenesis, as shown by pathway enrichment analysis. Among the DEGs, the top 15 hub genes were identified from the PPI network. Notably, the same bioinformatic procedures were conducted in 62 non-AD individuals (serving as controls of AD patients in the four included studies) with distinctly different findings from AD patients, indicating different regulatory mechanisms of lifespan between non-AD controls and AD, reconfirming the necessity of the present study.\nConclusion: These results shed some lights on lifespan-related regulatory mechanisms in AD patients, which also indicated that AD heterogeneity should be more taken into account in future investigations.", "claims": [{"id": "claim-method", "statement": "The meta p values of the DEGs were calculated using the R package of Robust Rank Aggregation (RRA) and the results were represented as meta-analysis scores (Kolde et al., 2012).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36909942", "locator": "sections[4] \"DEGs identification\" paragraph 2", "quote": "The meta p values of the DEGs were calculated using the R package of Robust Rank Aggregation (RRA) and the results were represented as meta-analysis scores (Kolde et al., 2012)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study are deposited in the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) repository, accession numbers: GSE48350, GSE5281, GSE28146, GSE36980.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36909942", "locator": "sections[15] \"Data availability statement\" paragraph 2", "quote": "The data presented in the study are deposited in the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) repository, accession numbers: GSE48350, GSE5281, GSE28146, GSE36980."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The meta-analysis identified 740 differentially expressed genes, comprising 361 upregulated and 379 downregulated genes, in longer-lived compared with shorter-lived Alzheimer's disease patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36909942", "locator": "sections[9] \"Identification of DEGs\" paragraph 3", "quote": "After meta-analysis, a list of 740 DEGs with 361 upregulated and 379 downregulated was identified in the AD group with longer lifespan compared to that with shorter lifespan."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The meta-analysis identified 740 differentially expressed genes, comprising 361 upregulated and 379 downregulated genes, in longer-lived compared with shorter-lived Alzheimer's disease patients.", "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:36909942"], "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:GSE28146"], "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:GSE28146"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36909942", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fnagi.2023.1072184", "sha256": 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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": ["GSE48350", "GSE5281", "GSE28146", "GSE36980"], "resolved_accessions": ["GSE48350", "GSE5281", "GSE28146", "GSE36980"], "statements": ["The data presented in the study are deposited in the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) repository, accession numbers: GSE48350, GSE5281, GSE28146, GSE36980."], "basis": "The paper names GSE48350, GSE5281, GSE28146, GSE36980 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36909942", "data:geo:GSE28146"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE28146"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:33:12Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13241, "completion_tokens": 1857, "cached_tokens": 256}}, "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:36909942", "type": "paper", "label": "pmid:36909942"}, {"id": "source:pmid:36909942", "type": "manuscript", "label": "PMID 36909942 full text"}, {"id": "data:geo:GSE28146", "type": "dataset", "label": "GEO GSE28146"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36909942", "type": "paper", "label": "pmid:36909942"}, {"id": "source:pmid:36909942", "type": "manuscript", "label": "PMID 36909942 full text"}, {"id": "data:geo:GSE28146", "type": "dataset", "label": "GEO GSE28146"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36909942", "type": "extraction", "used": ["source:pmid:36909942"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE28146", "type": "accession_resolution", "used": ["data:geo:GSE28146"], "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:36909942", "parent_hash": "sha256:be1e2bb526a0e3a59d3bccff7709fd4699c160904f62b0f005b3b087d1c50ec3", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE28146 licence not read", "asset:data:geo:GSE28146 not downloaded", "asset:data:geo:GSE36980 licence not read", "asset:data:geo:GSE36980 not downloaded", "asset:data:geo:GSE48350 licence not read", "asset:data:geo:GSE48350 not downloaded", "asset:data:geo:GSE5281 licence not read", "asset:data:geo:GSE5281 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": ["The meta p values of the DEGs were calculated using the R package of Robust Rank Aggregation (RRA) and the results were represented as meta-analysis scores (Kolde et al., 2012)."], "order_basis": "analysis_only", "id": "assay:1"}]}