Bioinformatics-based identification of CTSS, DOK2, and ENTPD1 as potential blood biomarkers of schizophrenia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39972407", "kind": "science-record", "revision": 4, "content_hash": "sha256:41ba2751a3d8f3bc9d89cff8d3dcf6ed370b952dba8db7fb91580bd0d83aa239", "created_at": "2026-11-01T20:30:13Z", "updated_at": "2026-11-01T22:56:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics-based identification of CTSS, DOK2, and ENTPD1 as potential blood biomarkers of schizophrenia.", "doi": "10.1186/s12888-025-06512-0", "pmid": "39972407", "authors": ["Lei Zhang", "Jiale Zhang", "Na Wang", "Chenwei Liu", "Shuting Wang", "Xiaotao Dong", "Lu Yang", "Xiaohong Bao", "Xiaobo Nie", "Jicheng Li"], "journal": "BMC psychiatry", "year": 2025, "abstract": "BACKGROUND: Although schizophrenia is a severe mental disorder that significantly impacts patients and society, there are currently no reliable blood-based biomarkers to assist in its diagnosis. The diagnosis primarily relies on clinical assessment and patient history, a method that is inherently subjective and prone to errors, potentially leading to diagnostic delays. In this study, we aim to utilize bioinformatics approaches to explore potential blood-based biomarkers for the diagnosis of schizophrenia. By employing advanced bioinformatics techniques, we hope to identify key genes and construct an effective diagnostic model, providing the clinic with a more objective and accurate diagnostic tool.\nMETHODS: In this research, we employed bioinformatics techniques to identify potential blood-based biomarkers for the diagnosis of schizophrenia. Initially, we selected schizophrenia-associated differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) database through the datasets GSE27383, GSE38484, and GSE38481. Subsequently, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on these DEGs to elucidate their biological functions and related pathways. Furthermore, we constructed a protein-protein interaction (PPI) network of the differentially expressed genes to identify key genes and matched them with their target microRNAs (miRNAs). In addition, we assessed the diagnostic potential of these key genes through immune infiltration analysis. The aim of this study is to reveal the roles of these hub genes in the pathogenesis of schizophrenia.\nRESULTS: Through bioinformatics analysis, we have identified three potential hub genes associated with the pathogenesis of schizophrenia: CTSS, DOK2, and ENTPD1. These genes are significantly correlated with the development of schizophrenia and may serve as promising diagnostic biomarkers for the condition.\nCONCLUSION: In this study, we have identified three pivotal genes-CTSS, DOK2, and ENTPD1-that are intimately associated with the pathogenesis of schizophrenia. The discovery of these genes not only enhances the precision of diagnostic efforts for schizophrenia but also provides a robust scientific foundation for the development of innovative treatment approaches for schizophrenia and related disorders. The identification of these biomarkers offers a tangible basis for early, accurate diagnosis, treatment, prognostic assessment, and rehabilitation evaluation in schizophrenia, potentially improving patients' quality of life and supporting the development of personalized therapeutics and antipsychotic medications.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were then discovered by differential analysis using the “limma” package(https://bioconductor.org/packages/release/bioc/html/limma.html) in R (R Core Team, Vienna, Austria).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39972407", "locator": "sections[2] \"Methods\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were then discovered by differential analysis using the “limma” package(https://bioconductor.org/packages/release/bioc/html/limma.html) in R (R Core Team, Vienna, Austria)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. These data were derived from the following resources available in the public domain [GSE27383: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383], [GSE38484: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38484], [GSE38481: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38481].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39972407", "locator": "sections[24] \"Data availability\" paragraph 2", "quote": "The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. These data were derived from the following resources available in the public domain [GSE27383: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383], [GSE38484: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38484], [GSE38481: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38481]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The combined diagnostic value of CTSS, DOK2, and ENTPD1 surpassed that of each individual hub gene.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39972407", "locator": "sections[16] \"Diagnostic evaluation of hub genes\" paragraph 2", "quote": "The AUC for all three hub genes combined surpassed those of the individual markers."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The combined diagnostic value of CTSS, DOK2, and ENTPD1 surpassed that of each individual hub gene.", "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:39972407"], "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:GSE27383"], "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:GSE27383"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39972407", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12888-025-06512-0", "sha256": "sha256:b9b9452599fc7241f57edcde92428bacc1a86adaf1d046d49565bd69d53461aa", "bytes": 49197, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12888-025-06512-0", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11841330", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE27383", "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=GSE27383", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27383", "version": null, "note": "The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. 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These data were derived from the following resources available in the public domain [GSE27383: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383], [GSE38484: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38484], [GSE38481: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38481].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM677118", "GSM677119", "GSM677120", "GSM677121", "GSM677122", "GSM677123", "GSM677124", "GSM677125", "GSM677126", "GSM677127", "GSM677128", "GSM677129", "GSM677130", "GSM677131", "GSM677132", "GSM677133", "GSM677134", "GSM677135", "GSM677136", "GSM677137", "GSM677138", "GSM677139", "GSM677140", "GSM677141", "GSM677142", "GSM677143", "GSM677144", "GSM677145", "GSM677146", "GSM677147", "GSM677148", "GSM677149", "GSM677150", "GSM677151", "GSM677152", "GSM677153", "GSM677154", "GSM677155", "GSM677156", "GSM677157", "GSM677158", "GSM677159", "GSM677160", "GSM677161", "GSM677162", "GSM677163", "GSM677164", "GSM677165", "GSM677166", "GSM677167", "GSM677168", "GSM677169", "GSM677170", "GSM677171", "GSM677172", "GSM677173", "GSM677174", "GSM677175", "GSM677176", "GSM677177", "GSM677178", "GSM677179", "GSM677180", "GSM677181", "GSM677182", "GSM677183", "GSM677184", "GSM677185", "GSM677186", "GSM677187", "GSM677188", "GSM677189"], "sample_count": 72, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Marked Reduction of AKT1 Expression and Deregulation of AKT1-associated Pathways in Peripheral Blood Mononuclear Cells of Schizophrenia Patients", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE38481", "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=GSE38481", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE38481", "version": null, "note": "The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. These data were derived from the following resources available in the public domain [GSE27383: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383], [GSE38484: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38484], [GSE38481: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38481].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. 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These data were derived from the following resources available in the public domain [GSE27383: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383], [GSE38484: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38484], [GSE38481: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38481].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. 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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": ["GSE27383", "GSE38484", "GSE38481"], "resolved_accessions": ["GSE27383", "GSE38484", "GSE38481"], "statements": ["The datasets generated and analysed during the current study are available in the [Gene Expression Omnibus] repository, [http://www.ncbi.nlm.nih.gov/geo/]. These data were derived from the following resources available in the public domain [GSE27383: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383], [GSE38484: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38484], [GSE38481: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38481]."], "basis": "The paper names GSE27383, GSE38484, GSE38481 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:39972407", "data:geo:GSE27383"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE27383"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:46:21Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13383, "completion_tokens": 1510, "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:39972407", "type": "paper", "label": "pmid:39972407"}, {"id": "source:pmid:39972407", "type": "manuscript", "label": "PMID 39972407 full text"}, {"id": "data:geo:GSE27383", "type": "dataset", "label": "GEO GSE27383"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39972407", "type": "paper", "label": "pmid:39972407"}, {"id": "source:pmid:39972407", "type": "manuscript", "label": "PMID 39972407 full text"}, {"id": "data:geo:GSE27383", "type": "dataset", "label": "GEO GSE27383"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39972407", "type": "extraction", "used": ["source:pmid:39972407"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE27383", "type": "accession_resolution", "used": ["data:geo:GSE27383"], "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:39972407", "parent_hash": "sha256:429545c30e9f00a00637aee8efebb0015ffa53d022d90c3b8b2adcda340ebdf3", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE27383 licence not read", "asset:data:geo:GSE27383 not downloaded", "asset:data:geo:GSE38481 licence not read", "asset:data:geo:GSE38481 not downloaded", "asset:data:geo:GSE38484 licence not read", "asset:data:geo:GSE38484 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": ["Differentially expressed genes (DEGs) were then discovered by differential analysis using the “limma” package(https://bioconductor.org/packages/release/bioc/html/limma.html) in R (R Core Team, Vienna, Austria)."], "order_basis": "analysis_only", "id": "assay:1"}]}