{"doi":"10.1101/2024.12.01.24318008","title":"Network-based drug repurposing for psychiatric disorders using single-cell genomics","abstract":"Neuropsychiatric disorders lack effective treatments due to a limited understanding of underlying cellular and molecular mechanisms. To address this, we integrated population-scale single-cell genomics data and analyzed cell-type-level gene regulatory networks across schizophrenia, bipolar disorder, and autism (23 cell classes/subclasses). Our analysis revealed potential druggable transcription factors co-regulating known risk genes that converge into cell-type-specific co-regulated modules. We applied graph neural networks on those modules to prioritize novel risk genes and leveraged them in a network-based drug repurposing framework to identify 220 drug molecules with the potential for targeting specific cell types. We found evidence for 37 of these drugs in reversing disorder-associated transcriptional phenotypes. Additionally, we discovered 335 drug-associated cell-type eQTLs, revealing genetic variation's influence on drug target expression at the cell-type level. Our results provide a single-cell network medicine resource that provides mechanistic insights for advancing treatment options for neuropsychiatric disorders.","journal":"medRxiv","year":2024,"id":489336,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991039,"name":"Noah Cohen Kalafut","orcid":"0000-0003-1421-0829","position":1,"is_corresponding":false},{"id":21380,"name":"Declan Clarke","orcid":"0000-0002-6128-7485","position":2,"is_corresponding":false},{"id":1036014,"name":"Jerome Choi","orcid":"0009-0008-7206-5758","position":3,"is_corresponding":false},{"id":1167171,"name":"Kalpana Hanthanan Arachchilage","orcid":"0000-0002-0849-9534","position":4,"is_corresponding":false},{"id":640878,"name":"Saniya Khullar","orcid":"0000-0002-4166-874X","position":5,"is_corresponding":false},{"id":415932,"name":"Yan Xia","orcid":"0000-0001-6432-9911","position":6,"is_corresponding":false},{"id":227468,"name":"Xiao Zhou","orcid":"0000-0002-8933-444X","position":7,"is_corresponding":false},{"id":108504,"name":"Mark Gerstein","orcid":"0000-0002-9746-3719","position":8,"is_corresponding":false},{"id":249243,"name":"Daifeng Wang","orcid":"0000-0001-9190-3704","position":9,"is_corresponding":false},{"id":21404,"name":"Chirag Gupta","orcid":"0000-0002-6121-7065","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:08:23.929823Z","pmid":"39677458","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":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}