Exploring Potential Biomarkers Underlying Pathogenesis of Alzheimer's Disease by Differential Co-expression Analysis.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30555656", "kind": "science-record", "revision": 4, "content_hash": "sha256:263f0fa3123a59ff68bb7916cfaf4bcb8818f4739f0091ac9953ec8774729f84", "created_at": "2026-11-01T15:40:39Z", "updated_at": "2026-11-01T21:21:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "partial", "title": "Exploring Potential Biomarkers Underlying Pathogenesis of Alzheimer's Disease by Differential Co-expression Analysis.", "doi": null, "pmid": "30555656", "authors": ["Fereshteh Izadi", "Mohammad Hasan Soheilifar"], "journal": "Avicenna journal of medical biotechnology", "year": 2018, "abstract": "BACKGROUND: Alzheimer's Disease (AD) is the most common form of dementia in the elderly. Due to the facts that biological causes of AD are complex in addition to increasing rates of AD worldwide, a deeper understanding of AD etiology is required for AD treatment and diagnosis.\nMETHODS: To identify molecular pathological alterations in AD brains, GSE36980 series containing microarray data samples from temporal cortex, frontal cortex and hippocampus were downloaded from Gene Expression Omnibus (GEO) database and valid gene symbols were subjected to building a gene co-expression network by a bioinformatics tool known as differential regulation from differential co-expression (DCGL) software package. Then, a network-driven integrative analysis was performed to find significant genes and underlying biological terms.\nRESULTS: A total of 17088 unique genes were parsed into three independent differential co-expression networks. As a result, a small number of differentially co-regulated genes mostly in frontal and hippocampus lobs were detected as potential biomarkers related to AD brains. Ultimately differentially co-regulated genes were enriched in biological terms including response to lipid and fatty acid and pathways mainly signaling pathway such as G-protein signaling pathway and glutamate receptor groups II and III. By conducting co-expression analysis, our study identified multiple genes that may play an important role in the pathogenesis of AD.\nCONCLUSION: The study aimed to provide a systematic understanding of the potential relationships among these genes and it is hoped that it could aid in AD biomarker discovery.", "claims": [{"id": "claim-method", "statement": "To find the significantly over-represented biological GO terms and functions of gene products within a co-expression network of DRGs and DRLs, functional classification was performed using BINGO Cytoscape plugin 16 running hypergeometric test and Benjamini & Hochberg FDR correction at significant level 0.01.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30555656", "locator": "sections[5] \"Gene ontology, pathway analysis and visualization\" paragraph 2", "quote": "To find the significantly over-represented biological GO terms and functions of gene products within a co-expression network of DRGs and DRLs, functional classification was performed using BINGO Cytoscape plugin 16 running hypergeometric test and Benjamini & Hochberg FDR correction at significant level 0.01."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The CEL files for GSE36980 series were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) database and normalized with RMA method by using the Linear Models for Microarray Data (limma) R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30555656", "locator": "sections[3] \"Data acquisition and pre-processing\" paragraph 2", "quote": "The CEL files for GSE36980 series were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) database and normalized with RMA method by using the Linear Models for Microarray Data (limma) R package."}], "state": "complete"}], "gaps": ["doi"]}, "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:30555656"], "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:30555656", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": null, "sha256": "sha256:b952a830bf698e1a6d2fbf0b01ba77cb504626f4d0dd459dfaa0b38e6460fa13", "bytes": 33826, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "30555656", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6252023", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:30555656:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:36d80493d2cbb3bb809ef4983f9016fa61756968b7518c0d43aa3f1e53df27bb", "bytes": 300, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#T1", "version": null, "note": "Sample characteristics", "structure": {"pmcid": "PMC6252023", "section_index": 3, "section_title": "Data acquisition and pre-processing", "row_count": 4, "column_count": 3}, "table": {"label": "Table 1.", "caption": "Sample characteristics", "rows": [["Biological samples", "Control", "AD patients"], ["Temporal cortex", "19", "10"], ["Frontal cortex", "18", "15"], ["Hippocampus", "10", "7"]], "row_count": 4, "column_count": 3, "numeric_cells": 6, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:30555656:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0608f54dfb63a7f0a6d69594ddf3fd85f7317ebdf431eb8843f528954dfd8ae0", "bytes": 3565, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#T2", "version": null, "note": "List of differential regulated genes (DRGs) and corresponding p-value<0.05 of differential co-expression enrichment (DCe) in temporal cortex, frontal cortex and hippocampus datasets", "structure": {"pmcid": "PMC6252023", "section_index": 7, "section_title": "Co-expression analysis", "row_count": 42, "column_count": 4}, "table": {"label": "Table 2.", "caption": "List of differential regulated genes (DRGs) and corresponding p-value<0.05 of differential co-expression enrichment (DCe) in temporal cortex, frontal cortex and hippocampus datasets", "rows": [["", "Gene name", "DCe p-value", "Description"], ["Temporal cortex", "ARID1A", "0.00069", "ARID1A was among down-regulated genes in AD model mice (17)"], ["Cdc42", "0.01224", "Cdc42 activity was increased in hippocampus neurons treated with fibrillary β-amyloid (18)"], ["LPPR4", "0.01395", "LPPR4 was up-regulated in incipient AD patients (19)"], ["PITHD1", "0.01863", "//"], ["SGIP1", "0.02064", "//"], ["SZT2", "0.01936", "//"], ["ZMPSTE24", "0.01936", "//"], [""], ["Frontal cortex", "CHD5", "5.19E-14", "The depletion of CHD5 was shown to be linked with AD associated gene sets (20)"], ["EFHD2", "3.00E-07", "EFhd2 has been found to be associated with aggregated tau in the brain in AD and in a mouse model of frontotemporal dementia (21,22)"], ["Prxs", "7.82E-07", "Peroxiredoxins (Prxs) may be associated with AD by reducing ROS elicited by amyloid β (Aβ) accumulation that could be a causative factor in the pathogenesis of AD (23)"], ["MAGIE3", "1.68E-06", "//"], ["EXTL1", "4.14E-06", "//"], ["HPCAL4", "2.09E-05", "HPCAL4 could be used as a prognostic marker for cognitive decline in AD (24)"], ["LPHN2", "2.59E-05", "LPHN2 is likely to be participated in AD as an altered protein in Lipid Raft (25)"], ["NIPAL3", "8.35E-05", "NIPAL3 was shown as a biomarker in Late-Onset Major Depressive Disorder (26)"], ["CACNA1E", "0.00017", "CACNA1E was down-regulated in cerebral Cockayne syndrome (27)"], ["IFI16", "0.00033", "IFI16 was participated in delaying onset of AD (28)"], ["HHLA3", "0.00122", "//"], ["KCNK1", "0.00202", "KCNK1 exhibited alternative splicing in patients with mesial temporal lobe epilepsy (29)"], ["rnpc3", "0.00384", "//"], ["DCAF6", "0.00542", "//"], ["IPO13", "0.00581", "IPO13 mutants involved in chronic inflammatory diseases (30)"], ["RPL11", "0.00585", "RPL11 revealed significant altered expression profiles in the neuron model of AD treated with rhTFAM (31)"], ["S100A1", "0.00716", "S100A1 modulates inflammation in AD (32)"], ["CNTN2", "0.02606", "CNTN2 associated with AD via BACE1 activity (33)"], ["GRIK3", "0.03774", "GRIK3 was highly expressed in major depression (34)"], [""], ["Hippocampus", "KCNK1", "1.55E-09", "//"], ["CHRNB2", "2.37E-09", "CHRNB2 was found to interfere with the immune system in neurologic disorders (35)"], ["HAPLN2", "3.43E-05", "Hapln2 has been recently shown to be accumulated in the neurofibrillary tangle of Alzheimer’s brain (36)"], ["Slc2a1", "0.00207", "Slc2a1 down-regulation exacerbated AD (37)"], ["FABP3", "0.00298", "serum levels of brain-type FABP are elevated in a significant proportion of patients with various neurodegenerative diseases including AD (38)"], ["DEGS1", "0.00327", "DEGS1 is likely to be involved in AD as an altered protein in Lipid Raft (25)"], ["NKAIN1", "0.00435", "//"], ["S100A1", "0.00434", "S100A1 modulates inflammation in AD (32)"], ["CNTN2", "0.00511", "CNTN2 associated with AD via b-Secretase (BACE1) activity (33)"], ["SFPQ", "0.00816", "SFPQ was shown as a transcription factor with an altered nucleo-cytoplasmic distribution under neurodegenerative conditions (39)"], ["GPSM2", "0.01073", "//"], ["GSTM1", "0.01591", "GSTM1 null genotype was found as risk factor for late-onset Alzheimer’s disease in Italian patients (40)"], ["CACHD1", "0.02830", "CACHD1 is a substrate of BACE1 responsible for generating the amyloid-b protein (41)"]], "row_count": 42, "column_count": 4, "numeric_cells": 73, "header_rows": 1, "locator": "section[7]/table-wrap[1]#T2"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "Hypergeometric test with Benjamini-Hochberg false discovery rate correction", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To find the significantly over-represented biological GO terms and functions of gene products within a co-expression network of DRGs and DRLs, functional classification was performed using BINGO Cytoscape plugin 16 running hypergeometric test and Benjamini & Hochberg FDR correction at significant level 0.01."}}], "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": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (Hypergeometric test with Benjamini-Hochberg false discovery rate correction), 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": "R4", "reachable": false, "accessions": ["GSE36980 series"], "resolved_accessions": [], "statements": ["The CEL files for GSE36980 series were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) database and normalized with RMA method by using the Linear Models for Microarray Data (limma) R package."], "basis": "The paper names GSE36980 series, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:30555656", "asset:table:pmid:30555656:1", "asset:table:pmid:30555656:2"], "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": "2026-10-31T18:13:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 25573, "completion_tokens": 869, "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:30555656", "type": "paper", "label": "pmid:30555656"}, {"id": "source:pmid:30555656", "type": "manuscript", "label": "PMID 30555656 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30555656", "type": "paper", "label": "pmid:30555656"}, {"id": "source:pmid:30555656", "type": "manuscript", "label": "PMID 30555656 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30555656", "type": "extraction", "used": ["source:pmid:30555656"], "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:30555656", "parent_hash": "sha256:657c68b9f21309798fcd9a5b19f4bb9fd055cb6a258a8085651c91a2fbfd188b", "fork_of": null, "generation": 3}, "gaps": ["doi", "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"]}