Unearthing of Key Genes Driving the Pathogenesis of Alzheimer's Disease via Bioinformatics.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33936168", "kind": "science-record", "revision": 7, "content_hash": "sha256:9b121b60e291e491c4d998422374f6844b2e5ba1503c450535c74c05a0b44ff6", "created_at": "2026-11-01T15:41:34Z", "updated_at": "2026-11-01T22:03:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unearthing of Key Genes Driving the Pathogenesis of Alzheimer's Disease via Bioinformatics.", "doi": "10.3389/fgene.2021.641100", "pmid": "33936168", "authors": ["Xingxing Zhao", "Hongmei Yao", "Xinyi Li"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Alzheimer's disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P < 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P < 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.", "claims": [{"id": "claim-method", "statement": "The WGCNA was completed by the R package “WGCNA” (Langfelder and Horvath, 2008, 2012).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33936168", "locator": "sections[4] \"Construction of Weighted Gene Coexpression Network Analysis\" paragraph 2", "quote": "The WGCNA was completed by the R package “WGCNA” (Langfelder and Horvath, 2008, 2012)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: GSE118553 and GSE131617 were collected from the NCBI GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33936168", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: GSE118553 and GSE131617 were collected from the NCBI GEO database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:33936168"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33936168", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.641100", "sha256": "sha256:ba024dd7062df39e126eb0454caeb6a4aa5a0d5bcd69dc4cc6d21da3e5a526de", "bytes": 47113, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.641100", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8085575", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33936168:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a9437f0bcfd69e38c8946cca38d77169578ada42554537563e1af1f8f0f39e7b", "bytes": 400, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#T1", "version": null, "note": "The information of GSE118553.", "structure": {"pmcid": "PMC8085575", "section_index": 3, "section_title": "Data Collection and Data Preprocessing", "row_count": 6, "column_count": 4}, "table": {"label": "TABLE 1", "caption": "The information of GSE118553.", "rows": [["Sample source", "AD", "Control", "AsymAD"], ["Temporal cortex (TC)", "52", "31", "32"], ["Frontal cortex (FC)", "40", "23", "33"], ["Entorhinal cortex (EC)", "37", "24", "37"], ["Cerebellum (CE)", "38", "22", "32"], ["Sum", "167", "100", "134"]], "row_count": 6, "column_count": 4, "numeric_cells": 15, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33936168:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:82e38fd6eefa5ca9da4ede23d552ace26a45815ff80b2aaf99bd3854bf26928f", "bytes": 399, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#T2", "version": null, "note": "The information of GSE131617 GPL5175.", "structure": {"pmcid": "PMC8085575", "section_index": 3, "section_title": "Data Collection and Data Preprocessing", "row_count": 6, "column_count": 3}, "table": {"label": "TABLE 2", "caption": "The information of GSE131617 GPL5175.", "rows": [["Braak NFT stage", "Sample source", "Samples"], ["0", "13 TC; 13 FC; 13 EC", "39"], ["I–II", "20 TC; 20 FC; 20 EC", "60"], ["III–IV", "19 TC; 19 FC; 19 EC", "57"], ["V–VI", "19 TC; 19 FC; 19 EC", "57"], ["–", "–", "213"]], "row_count": 6, "column_count": 3, "numeric_cells": 10, "header_rows": 1, "locator": "section[3]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:33936168:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6f59f584c207ed08882b2a0c445c7dc38d8542e377f4bc976044d166b1b4e736", "bytes": 741, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#T3", "version": null, "note": "The hyperparameter tuning of 10 machine learning classifiers.", "structure": {"pmcid": "PMC8085575", "section_index": 8, "section_title": "Validation of Significant Hub Genes by Machine Learning", "row_count": 11, "column_count": 2}, "table": {"label": "TABLE 3", "caption": "The hyperparameter tuning of 10 machine learning classifiers.", "rows": [["Classifiers", "Parameter"], ["SVM", "kernel = ‘linear’, probability = True, Random_state = 42"], ["Random forest", "Random_state = 42"], ["Extra trees", "Random_state = 42"], ["AdaBoost", "DecisionTreeClassifier (random_state = 42), Random_state = 42, learning_rate = 0.1"], ["Gradient boosting", "Random_state = 42"], ["MLP classifier", "Random_state = 42"], ["K neighbors", "Default configuration"], ["Logistic regression", "Random_state = 42"], ["Linear discriminant analysis", "Default configuration"], ["Gaussian NB", "Default configuration"]], "row_count": 11, "column_count": 2, "numeric_cells": 7, "header_rows": 1, "locator": "section[8]/table-wrap[1]#T3"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-2", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-3", "family": null, "specific": null, "label": "weighted gene coexpression network analysis (WGCNA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The WGCNA was completed by the R package “WGCNA” (Langfelder and Horvath, 2008, 2012)."}}], "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": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: GSE118553 and GSE131617 were collected from the NCBI GEO database."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:33936168", "asset:table:pmid:33936168:1", "asset:table:pmid:33936168:2", "asset:table:pmid:33936168:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:33:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 33519, "completion_tokens": 1233, "cached_tokens": 11272}}, "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:33936168", "type": "paper", "label": "pmid:33936168"}, {"id": "source:pmid:33936168", "type": "manuscript", "label": "PMID 33936168 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33936168", "type": "paper", "label": "pmid:33936168"}, {"id": "source:pmid:33936168", "type": "manuscript", "label": "PMID 33936168 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33936168", "type": "extraction", "used": ["source:pmid:33936168"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:33936168", "parent_hash": "sha256:511beee01317d9b7947c7d8312c7f9f3408f434c53dc15eb7f19357dac0be095", "fork_of": null, "generation": 6}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["ANOVA"], "order_basis": "analysis_only", "id": "assay:1"}]}