Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between Porphyromonas gingivalis (P. gingivalis) and Alzheimer's Disease (AD).

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36982508", "kind": "science-record", "revision": 4, "content_hash": "sha256:dee67ad5b0848df4f380b9a65e9acaa0ab23cb2a4a2447085f0263f89fa82a0d", "created_at": "2026-11-01T19:01:38Z", "updated_at": "2026-11-01T22:51:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between Porphyromonas gingivalis (P. gingivalis) and Alzheimer's Disease (AD).", "doi": "10.3390/ijms24065432", "pmid": "36982508", "authors": ["Ahmed Hamarsha", "Kumarendran Balachandran", "Ahmad Tarmidi Sailan", "Nurrul Shaqinah Nasruddin"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "The association between Porphyromonas gingivalis (P. gingivalis) and Alzheimer's disease (AD) remains unclear. The major aim of this study was to elucidate the role of genes and molecular targets in P. gingivalis-associated AD. Two Gene Expression Omnibus (GEO) datasets, GSE5281 for AD (n = 84 Alzheimer's, n = 74 control) and GSE9723 (n = 4 P. gingivalis, n = 4 control), were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained, and genes common to both diseases were drawn. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed from the top 100 genes (50 upregulated and 50 downregulated genes). We then proceeded with CMap analysis to screen for possible small drug molecules targeting these genes. Subsequently, we performed molecular dynamics simulations. A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a p-value < 0.05. The PPI network of the top 100 genes showed UCHL1, SST, CHGB, CALY, and INA to be common in the MCC, DMNC, and MNC domains. Out of the 10 common genes identified, only 1 was mapped in CMap. We found three candidate small drug molecules to be a fit for PLK2, namely PubChem ID: 24971422, 11364421, and 49792852. We then performed molecular docking of PLK2 with PubChem ID: 24971422, 11364421, and 49792852. The best target, 11364421, was used to conduct the molecular dynamics simulations. The results of this study unravel novel genes to P. gingivalis-associated AD that warrant further validation.", "claims": [{"id": "claim-method", "statement": "Using the limma package in R, we identified the differentially expressed genes (DEGs) between AD and P. gingivalis. The criteria of p < 0.05 and log2FC > 1 were set before entering to VENN tool to visualise the intersecting genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36982508", "locator": "sections[16] \"4.3. DEGs Screening\" paragraph 2", "quote": "Using the limma package in R, we identified the differentially expressed genes (DEGs) between AD and P. gingivalis. The criteria of p < 0.05 and log2FC > 1 were set before entering to VENN tool to visualise the intersecting genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Not Applicable.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36982508", "locator": "sections[23] \"Institutional Review Board Statement\" paragraph 2", "quote": "Not Applicable."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a p-value < 0.05.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a p-value < 0.05."}, "evidence": [{"asset": "source:pmid:36982508", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a p-value < 0.05."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a p-value < 0.05.", "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:36982508"], "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:GSE5281"], "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:GSE5281"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36982508", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/ijms24065432", "sha256": "sha256:19b70fcb60dfaf30c72426f48ca1715361ac0060cfbf631a0978865f4bebf9fd", "bytes": 40293, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/ijms24065432", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10049565", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE5281", "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=GSE5281", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5281", "version": null, "note": "Not Applicable.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Not Applicable.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM119615", "GSM119616", "GSM119617", "GSM119618", "GSM119619", "GSM119620", "GSM119621", "GSM119622", "GSM119623", "GSM119624", "GSM119625", "GSM119626", "GSM119627", "GSM119628", "GSM119629", "GSM119630", "GSM119631", "GSM119632", "GSM119633", "GSM119634", "GSM119635", "GSM119636", "GSM119637", "GSM119638", "GSM119639", "GSM119640", "GSM119641", "GSM119642", "GSM119643", "GSM119644", "GSM119645", "GSM119646", "GSM119647", "GSM119648", "GSM119649", "GSM119650", "GSM119651", "GSM119652", "GSM119653", "GSM119654", "GSM119655", "GSM119656", "GSM119657", "GSM119658", "GSM119659", "GSM119660", "GSM119661", "GSM119662", "GSM119663", "GSM119664", "GSM119665", "GSM119666", "GSM119667", "GSM119668", "GSM119669", "GSM119670", "GSM119671", "GSM119672", "GSM119673", "GSM119674", "GSM119675", "GSM119676", "GSM119677", "GSM119678", "GSM119679", "GSM119680", "GSM119681", "GSM119682", "GSM119683", "GSM119684", "GSM119685", "GSM119686", "GSM119687", "GSM119688", "GSM238763", "GSM238790", "GSM238791", "GSM238792", "GSM238793", "GSM238794", "GSM238795", "GSM238796", "GSM238797", "GSM238798", "GSM238799", "GSM238800", "GSM238801", "GSM238802", "GSM238803", "GSM238804", "GSM238805", "GSM238806", "GSM238807", "GSM238808", "GSM238809", "GSM238810", "GSM238811", "GSM238812", "GSM238813", "GSM238815", "GSM238816", "GSM238817", "GSM238818", "GSM238819", "GSM238820", "GSM238821", "GSM238822", "GSM238823", "GSM238824", "GSM238825", "GSM238826", "GSM238827", "GSM238834", "GSM238835", "GSM238837", "GSM238838", "GSM238839", "GSM238840", "GSM238841", "GSM238842", "GSM238843", "GSM238844", "GSM238845", "GSM238846", "GSM238847", "GSM238848", "GSM238851", "GSM238854", "GSM238855", "GSM238856", "GSM238857", "GSM238858", "GSM238860", "GSM238861", "GSM238862", "GSM238863", "GSM238864", "GSM238865", "GSM238867", "GSM238868", "GSM238870", "GSM238871", "GSM238872", "GSM238873", "GSM238874", "GSM238875", "GSM238877", "GSM238941", "GSM238942", "GSM238943", "GSM238944", "GSM238945", "GSM238946", "GSM238947", "GSM238948", "GSM238949", "GSM238951", "GSM238952", "GSM238953", "GSM238955", "GSM238963"], "sample_count": 161, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Alzheimer's disease and the normal aged brain (steph-affy-human-433773)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE9723", "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=GSE9723", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE9723", "version": null, "note": "Not Applicable.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Not Applicable.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM245725", "GSM245726", "GSM245727", "GSM245728", "GSM245729", "GSM245730", "GSM245731", "GSM245732", "GSM245733", "GSM245734", "GSM245735", "GSM245736"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Gingival Epithelial Cell Transcriptional Responses to Pathogenic Oral Microbial Species.", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE5281 not downloaded", "asset:data:geo:GSE5281 licence not read", "asset:data:geo:GSE9723 not downloaded", "asset:data:geo:GSE9723 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Using the limma package in R, we identified the differentially expressed genes (DEGs) between AD and P. gingivalis. The criteria of p < 0.05 and log2FC > 1 were set before entering to VENN tool to visualise the intersecting genes."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 0.05, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE5281", "GSE9723"], "resolved_accessions": ["GSE5281", "GSE9723"], "statements": ["Not Applicable."], "basis": "The paper names GSE5281, GSE9723 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:36982508", "data:geo:GSE5281"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE5281"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:35:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12825, "completion_tokens": 1323, "cached_tokens": 128}}, "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:36982508", "type": "paper", "label": "pmid:36982508"}, {"id": "source:pmid:36982508", "type": "manuscript", "label": "PMID 36982508 full text"}, {"id": "data:geo:GSE5281", "type": "dataset", "label": "GEO GSE5281"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36982508", "type": "paper", "label": "pmid:36982508"}, {"id": "source:pmid:36982508", "type": "manuscript", "label": "PMID 36982508 full text"}, {"id": "data:geo:GSE5281", "type": "dataset", "label": "GEO GSE5281"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36982508", "type": "extraction", "used": ["source:pmid:36982508"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE5281", "type": "accession_resolution", "used": ["data:geo:GSE5281"], "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:36982508", "parent_hash": "sha256:bb898e4f77603b3d31f7f2979ceb7bc0f39bf53942069186679cf47a2ec997af", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE5281 licence not read", "asset:data:geo:GSE5281 not downloaded", "asset:data:geo:GSE9723 licence not read", "asset:data:geo:GSE9723 not downloaded", "execution.not_run", "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": ["Using the limma package in R, we identified the differentially expressed genes (DEGs) between AD and P. gingivalis. The criteria of p < 0.05 and log2FC > 1 were set before entering to VENN tool to visualise the intersecting genes."], "order_basis": "analysis_only", "id": "assay:1"}]}