Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37872602", "kind": "science-record", "revision": 4, "content_hash": "sha256:69bf5cc4f1622ce330c3dd379279d1485fd53bbf7ff046401a803f286e1b7deb", "created_at": "2026-11-01T19:02:44Z", "updated_at": "2026-11-01T22:10:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.", "doi": "10.1186/s13023-023-02953-6", "pmid": "37872602", "authors": ["Woosub Shin", "Martina Kutmon", "Eleni Mina", "Therese van Amelsvoort", "Chris T Evelo", "Friederike Ehrhart"], "journal": "Orphanet journal of rare diseases", "year": 2023, "abstract": "BACKGROUND: 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency. Many characteristics of the disorder are known, such as the phenotypic variability of the disease and the biological processes associated with it; however, the exact and systemic molecular mechanisms between the deleted area and its resulting clinical phenotypic expression, for example that of neuropsychiatric diseases, are not yet fully understood.\nRESULTS: Using previously published transcriptomics data (GEO:GSE59216), we constructed two datasets: one set compares 22q11DS patients experiencing neuropsychiatric diseases versus healthy controls, and the other set 22q11DS patients without neuropsychiatric diseases versus healthy controls. We modified and applied the pathway interaction method, originally proposed by Kelder et al. (2011), on a network created using the WikiPathways pathway repository and the STRING protein-protein interaction database. We identified genes and biological processes that were exclusively associated with the development of neuropsychiatric diseases among the 22q11DS patients. Compared with the 22q11DS patients without neuropsychiatric diseases, patients experiencing neuropsychiatric diseases showed significant overrepresentation of regulated genes involving the natural killer cell function and the PI3K/Akt signalling pathway, with affected genes being closely associated with downregulation of CRK like proto-oncogene adaptor protein. Both the pathway interaction and the pathway overrepresentation analysis observed the disruption of the same biological processes, even though the exact lists of genes collected by the two methods were different.\nCONCLUSIONS: Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients. This way, our method was able to complement the pathway overrepresentation analysis, by filling the knowledge gaps on how the affected pathways are linked to the original deletion on chromosome 22. We expect our pathway interaction method could be used for problems with similar contexts, where complex genetic mechanisms need to be identified to explain the resulting phenotypic plasticity.", "claims": [{"id": "claim-method", "statement": "In this study, we re-analysed a transcriptomics dataset originally created by Jalbrzikowski et al. [37] using a novel pathway interaction analysis method to identify paths between the causative genes for this disorder and the differentially expressed genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37872602", "locator": "sections[2] \"Results\" paragraph 2", "quote": "In this study, we re-analysed a transcriptomics dataset originally created by Jalbrzikowski et al. [37] using a novel pathway interaction analysis method to identify paths between the causative genes for this disorder and the differentially expressed genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data was taken from a previously published study by Jalbrzikowski et al., with GEO accession number GSE59216. The analysis scripts can be found under https://github.com/woosubs/PathwayInteraction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37872602", "locator": "sections[17] \"Data Availability\" paragraph 2", "quote": "The data was taken from a previously published study by Jalbrzikowski et al., with GEO accession number GSE59216. The analysis scripts can be found under https://github.com/woosubs/PathwayInteraction."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37872602", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS 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:37872602"], "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:GSE59216"], "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:GSE59216"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37872602", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13023-023-02953-6", "sha256": "sha256:bea5aa3d30575cbd0b2965ab16350144770edbb5705cf19c9ce8515e47cb657c", "bytes": 60061, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13023-023-02953-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10594698", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE59216", "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=GSE59216", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE59216", "version": null, "note": "The data was taken from a previously published study by Jalbrzikowski et al., with GEO accession number GSE59216. The analysis scripts can be found under https://github.com/woosubs/PathwayInteraction.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data was taken from a previously published study by Jalbrzikowski et al., with GEO accession number GSE59216. The analysis scripts can be found under https://github.com/woosubs/PathwayInteraction.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1430750", "GSM1430751", "GSM1430752", "GSM1430753", "GSM1430754", "GSM1430755", "GSM1430756", "GSM1430757", "GSM1430758", "GSM1430759", "GSM1430760", "GSM1430761", "GSM1430762", "GSM1430763", "GSM1430764", "GSM1430765", "GSM1430766", "GSM1430767", "GSM1430768", "GSM1430769", "GSM1430770", "GSM1430771", "GSM1430772", "GSM1430773", "GSM1430774", "GSM1430775", "GSM1430776", "GSM1430777", "GSM1430778", "GSM1430779", "GSM1430780", "GSM1430781", "GSM1430782", "GSM1430783", "GSM1430784", "GSM1430785", "GSM1430786", "GSM1430787", "GSM1430788", "GSM1430789", "GSM1430790", "GSM1430791", "GSM1430792", "GSM1430793", "GSM1430794", "GSM1430795", "GSM1430796", "GSM1430797", "GSM1430798", "GSM1430799", "GSM1430800", "GSM1430801", "GSM1430802", "GSM1430803", "GSM1430804", "GSM1430805", "GSM1430806", "GSM1430807", "GSM1430808", "GSM1430809", "GSM1430810", "GSM1430811", "GSM1430812", "GSM1430813", "GSM1430814", "GSM1430815", "GSM1430816", "GSM1430817", "GSM1430818", "GSM1430819", "GSM1430820", "GSM1430821", "GSM1430822", "GSM1430823", "GSM1430824", "GSM1430825", "GSM1430826", "GSM1430827", "GSM1430828", "GSM1430829", "GSM1430830", "GSM1430831", "GSM1430832", "GSM1430833", "GSM1430834", "GSM1430835", "GSM1430836", "GSM1430837", "GSM1430838", "GSM1430839", "GSM1430840", "GSM1430841", "GSM1430842", "GSM1430843", "GSM1430844", "GSM1430845", "GSM1430846", "GSM1430847", "GSM1430848", "GSM1430849", "GSM1430850", "GSM1430851", "GSM1430852", "GSM1430853", "GSM1430854", "GSM1430855", "GSM1430856", "GSM1430857", "GSM1430858", "GSM1430859", "GSM1430860", "GSM1430861"], "sample_count": 112, "group_sizes": null, "group_sizes_basis": null, "platform": "6947;10558", "taxon": "Homo sapiens", "title": "Genome-wide transcription profiling of 22q11.2 deletion syndrome reveals functional pathways related to phenotypic expression of psychosis and autism spectrum disorder", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE59216 not downloaded", "asset:data:geo:GSE59216 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": "protein-protein interaction"}}, {"id": "method-2", "family": null, "specific": null, "label": "pathway interaction analysis method", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "In this study, we re-analysed a transcriptomics dataset originally created by Jalbrzikowski et al. [37] using a novel pathway interaction analysis method to identify paths between the causative genes for this disorder and the differentially expressed genes."}}], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE59216"], "resolved_accessions": ["GSE59216"], "statements": ["The data was taken from a previously published study by Jalbrzikowski et al., with GEO accession number GSE59216. The analysis scripts can be found under https://github.com/woosubs/PathwayInteraction."], "basis": "The paper names GSE59216 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:37872602", "data:geo:GSE59216"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE59216"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:57:02Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16229, "completion_tokens": 1225, "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:37872602", "type": "paper", "label": "pmid:37872602"}, {"id": "source:pmid:37872602", "type": "manuscript", "label": "PMID 37872602 full text"}, {"id": "data:geo:GSE59216", "type": "dataset", "label": "GEO GSE59216"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37872602", "type": "paper", "label": "pmid:37872602"}, {"id": "source:pmid:37872602", "type": "manuscript", "label": "PMID 37872602 full text"}, {"id": "data:geo:GSE59216", "type": "dataset", "label": "GEO GSE59216"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37872602", "type": "extraction", "used": ["source:pmid:37872602"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE59216", "type": "accession_resolution", "used": ["data:geo:GSE59216"], "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:37872602", "parent_hash": "sha256:e30b96db666e5a2d7616126f91f231ef7c9c165fc3140814b249fcb0f8f1e428", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE59216 licence not read", "asset:data:geo:GSE59216 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "analysis_only", "id": "assay:1"}]}