{"doi":"10.1101/2022.08.31.22279406","title":"Single-cell multi-cohort dissection of the schizophrenia transcriptome","abstract":"Schizophrenia is a prevalent mental illness with a high societal burden, complex pathophysiology, and diverse genetic and environmental etiology. Its complexity, polygenicity, and heterogeneity have hindered mechanistic elucidation and the search for new therapeutics. We present a single-cell dissection of schizophrenia-associated transcriptomic changes in the human prefrontal cortex across two independent cohorts, one deeply profiling 48 subjects (361,996 cells), and the other broadly profiling 92 subjects (106,761 cells). We identified 25 cell types that we used to produce a high-resolution atlas of schizophrenia-altered genes and pathways. Excitatory neurons were the most affected cell group, with transcriptional changes converging on neurodevelopment and synapse-related molecular pathways. Differentially expressed gene sets implicate a coherently expressed module of trans-acting regulatory factors involved in neurodevelopment and genetically associated with schizophrenia risk. Transcriptional alterations significantly overlapped with known genetic risk factors, suggesting convergence of rare and common genomic variants on reproducible neuronal population specific alterations in schizophrenia. The severity of transcriptional pathology segregated two populations of schizophrenia subjects in a manner consistent with the expression of specific transcriptional patterns marked by genes involved in synaptic function and chromatin dynamics. Our results provide a high-resolution single cell atlas linking transcriptomic changes within specific cell populations to etiological genetic risk factors, contextualizing established knowledge within the cytoarchitecture of the human cortex and facilitating mechanistic understanding of schizophrenia pathophysiology and heterogeneity.","journal":null,"year":2022,"id":143,"datarank":0.8986122131017131,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.3884326058523897,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.3884326058523897,"corpus_percentile":57.20097640358015,"corpus_rank":527,"citation_count":29,"citer_count":21,"citers_with_citation_signal":18,"citers_with_endowment":18,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5201,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-09-02","fair_score":14.5833,"fair_percentile":1.2752858399296394,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1190,"name":"Shahin Mohammadi","orcid":"0000-0001-8734-2326","position":1,"is_corresponding":false},{"id":21393,"name":"Prashant S. Emani","orcid":"0000-0002-3091-5231","position":2,"is_corresponding":false},{"id":1192,"name":"Jose Davila-Velderrain","orcid":null,"position":3,"is_corresponding":false},{"id":1193,"name":"Sivan Subburaju","orcid":"0000-0003-3111-9859","position":4,"is_corresponding":false},{"id":1194,"name":"Daniel Reed Tso","orcid":null,"position":5,"is_corresponding":false},{"id":1195,"name":"Makayla Hourihan","orcid":null,"position":6,"is_corresponding":false},{"id":1196,"name":"Shan Jiang","orcid":"0000-0002-9791-1593","position":7,"is_corresponding":false},{"id":1197,"name":"Hao-Chih Lee","orcid":"0000-0002-1538-6175","position":8,"is_corresponding":false},{"id":21366,"name":"Brian J. Beliveau","orcid":"0000-0003-1314-3118","position":9,"is_corresponding":false},{"id":1200,"name":"Georgios Voloudakis","orcid":"0000-0002-5729-632X","position":11,"is_corresponding":false},{"id":1201,"name":"Vahram Haroutunian","orcid":"0000-0001-5860-2512","position":12,"is_corresponding":false},{"id":1202,"name":"Gabriel E. Hoffman","orcid":"0000-0002-0957-0224","position":13,"is_corresponding":false},{"id":1203,"name":"Panos Roussos","orcid":"0000-0002-4640-6239","position":14,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":15,"is_corresponding":false},{"id":1204,"name":"José Dávila-Velderrain","orcid":"0000-0003-0271-6267","position":16,"is_corresponding":false},{"id":1189,"name":"W. Brad Ruzicka","orcid":"0000-0001-6749-4875","position":0,"is_corresponding":true}],"reference_count":132,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":20.0,"fair_a":30.0,"fair_i":0.0,"fair_r":8.3333,"fair_zscore":-2.7705,"fair_rationale":{"fair_score":14.58,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":20.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"datacite=0, pmcid=False, pmid=False","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"No machine-readable metadata or structured metadata are provided; the paper only includes a DOI for the preprint itself."}]},"A":{"name":"Accessible","score":30.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"No clear data or code access protocol is stated; the paper asserts 'All rights reserved. No reuse allowed without permission.' which restricts access."}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"No mention of standard formats, vocabularies, or persistent identifiers beyond standard gene symbols; no evidence of community standards."}]},"R":{"name":"Reusable","score":8.33,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.0,"signal":null,"rationale":"No data-availability statement, no license (restrictive), and no explicit measures for reproducibility beyond detailed methods; data and code are not publicly accessible."}]}},"suggestions":["Deposit raw and processed single-cell RNA-seq data in a public repository (e.g., GEO, ArrayExpress) with a persistent identifier.","Provide a clear data-availability statement and an open license (e.g., CC0 or CC-BY) to allow reuse.","Include machine-readable metadata (e.g., structured data description in JSON-LD or RDF) to enhance findability.","Use standard file formats (e.g., HDF5, MEX) and community vocabularies (e.g., Cell Ontology) for interoperability.","Make analysis code available in a public repository (e.g., GitHub) with a software license and documentation for reproducibility."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"unpaywall_pdf"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"unpaywall_pdf","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:45:33.412291Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}