Bioinformatics investigation on blood-based gene expressions of Alzheimer's disease revealed ORAI2 gene biomarker susceptibility: An explainable artificial intelligence-based approach.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36809524", "kind": "science-record", "revision": 2, "content_hash": "sha256:807e2a1542dc388965d976a7aa18be85cc2cedc4068ba3e1d0ea0ff1016cd940", "created_at": "2026-11-01T19:01:23Z", "updated_at": "2026-11-01T21:30:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics investigation on blood-based gene expressions of Alzheimer's disease revealed ORAI2 gene biomarker susceptibility: An explainable artificial intelligence-based approach.", "doi": "10.1007/s11011-023-01171-0", "pmid": "36809524", "authors": ["Karthik Sekaran", "Alsamman M Alsamman", "C George Priya Doss", "Hatem Zayed"], "journal": "Metabolic brain disease", "year": 2023, "abstract": "The progressive, chronic nature of Alzheimer's disease (AD), a form of dementia, defaces the adulthood of elderly individuals. The pathogenesis of the condition is primarily unascertained, turning the treatment efficacy more arduous. Therefore, understanding the genetic etiology of AD is essential to identifying targeted therapeutics. This study aimed to use machine-learning techniques of expressed genes in patients with AD to identify potential biomarkers that can be used for future therapy. The dataset is accessed from the Gene Expression Omnibus (GEO) database (Accession Number: GSE36980). The subgroups (AD blood samples from frontal, hippocampal, and temporal regions) are individually investigated against non-AD models. Prioritized gene cluster analyses are conducted with the STRING database. The candidate gene biomarkers were trained with various supervised machine-learning (ML) classification algorithms. The interpretation of the model prediction is perpetrated with explainable artificial intelligence (AI) techniques. This experiment revealed 34, 60, and 28 genes as target biomarkers of AD mapped from the frontal, hippocampal, and temporal regions. It is identified ORAI2 as a shared biomarker in all three areas strongly associated with AD's progression. The pathway analysis showed that STIM1 and TRPC3 are strongly associated with ORAI2. We found three hub genes, TPI1, STIM1, and TRPC3, in the network of the ORAI2 gene that might be involved in the molecular pathogenesis of AD. Naive Bayes classified the samples of different groups by fivefold cross-validation with 100% accuracy. AI and ML are promising tools in identifying disease-associated genes that will advance the field of targeted therapeutics against genetic diseases.", "claims": [{"id": "claim-method", "statement": "GEO2R was used to compare two groups of gene expression data, healthy and AD cases, across three different brain regions samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36809524", "locator": "sections[4] \"Gene expression data collection and analysis\" paragraph 2", "quote": "GEO2R was used to compare two groups of gene expression data, healthy and AD cases, across three different brain regions samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data are available with the corresponding author GPDC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36809524", "locator": "sections[16] \"Data availability\" paragraph 2", "quote": "The data are available with the corresponding author GPDC."}], "state": "complete"}, {"id": "claim-target-result", "statement": "It is identified ORAI2 as a shared biomarker in all three areas strongly associated with AD's progression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36809524", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "This experiment revealed 34, 60, and 28 genes as target biomarkers of AD mapped from the frontal, hippocampal, and temporal regions."}, {"asset": "source:pmid:36809524", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "It is identified ORAI2 as a shared biomarker in all three areas strongly associated with AD's progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "It is identified ORAI2 as a shared biomarker in all three areas strongly associated with AD's progression.", "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:36809524"], "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:GSE36980"], "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:GSE36980"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36809524", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s11011-023-01171-0", "sha256": "sha256:faee8e0df2d735a42d4dc9914ef70bbced848ff9b41df19a3a36d3399c246944", "bytes": 41862, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s11011-023-01171-0", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9942063", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE36980", "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=GSE36980", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE36980", "version": null, "note": "The data are available with the corresponding author GPDC.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data are available with the corresponding author GPDC.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4764672", "GSM907792", "GSM907793", "GSM907794", "GSM907795", "GSM907796", "GSM907797", "GSM907798", "GSM907799", "GSM907800", "GSM907801", "GSM907802", "GSM907803", "GSM907804", "GSM907805", "GSM907806", "GSM907807", "GSM907808", "GSM907809", "GSM907810", "GSM907811", "GSM907812", "GSM907813", "GSM907814", "GSM907815", "GSM907816", "GSM907817", "GSM907818", "GSM907819", "GSM907820", "GSM907821", "GSM907822", "GSM907823", "GSM907824", "GSM907825", "GSM907826", "GSM907827", "GSM907828", "GSM907829", "GSM907830", "GSM907831", "GSM907832", "GSM907833", "GSM907834", "GSM907835", "GSM907836", "GSM907837", "GSM907838", "GSM907839", "GSM907840", "GSM907841", "GSM907842", "GSM907843", "GSM907844", "GSM907845", "GSM907846", "GSM907847", "GSM907848", "GSM907849", "GSM907850", "GSM907851", "GSM907852", "GSM907853", "GSM907854", "GSM907855", "GSM907856", "GSM907857", "GSM907858", "GSM907859", "GSM907860", "GSM907861", "GSM907862", "GSM907863", "GSM907864", "GSM907865", "GSM907866", "GSM907867", "GSM907868", "GSM907869", "GSM907870"], "sample_count": 80, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Expression data from post mortem Alzheimer's disease brains", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE36980 not downloaded", "asset:data:geo:GSE36980 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "GEO2R differential gene expression analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "GEO2R was used to compare two groups of gene expression data, healthy and AD cases, across three different brain regions samples."}}], "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": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (GEO2R differential gene expression analysis), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "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": ["GSE36980"], "resolved_accessions": ["GSE36980"], "statements": ["The data are available with the corresponding author GPDC."], "basis": "The paper names GSE36980 in NCBI-GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:36809524", "data:geo:GSE36980"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE36980"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:27:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11708, "completion_tokens": 1561, "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:36809524", "type": "paper", "label": "pmid:36809524"}, {"id": "source:pmid:36809524", "type": "manuscript", "label": "PMID 36809524 full text"}, {"id": "data:geo:GSE36980", "type": "dataset", "label": "GEO GSE36980"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36809524", "type": "paper", "label": "pmid:36809524"}, {"id": "source:pmid:36809524", "type": "manuscript", "label": "PMID 36809524 full text"}, {"id": "data:geo:GSE36980", "type": "dataset", "label": "GEO GSE36980"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36809524", "type": "extraction", "used": ["source:pmid:36809524"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE36980", "type": "accession_resolution", "used": ["data:geo:GSE36980"], "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:36809524", "parent_hash": "sha256:44aa360fb941718ab3ccccd0d523f1bc8d7ffd2b92d6c8fffe6f7695db0d5985", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE36980 licence not read", "asset:data:geo:GSE36980 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"]}