{"doi":"10.1101/2023.11.30.569494","title":"Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional transcriptional circuits","abstract":"Abstract Pooled optical screens have enabled the study of cellular interactions, morphology, or dynamics at massive scale, but have not yet leveraged the power of highly-plexed single-cell resolved transcriptomic readouts to inform molecular pathways. Here, we present Perturb-FISH, which bridges these approaches by combining imaging spatial transcriptomics with parallel optical detection of in situ amplified guide RNAs. We show that Perturb-FISH recovers intracellular effects that are consistent with Perturb-seq results in a screen of lipopolysaccharide response in cultured monocytes, and uncover new intercellular and density-dependent regulation of the innate immune response. We further pair Perturb-FISH with a functional readout in a screen of autism spectrum disorder risk genes, showing common calcium activity phenotypes in induced pluripotent stem cell derived astrocytes and their associated genetic interactions and dysregulated molecular pathways. Perturb-FISH is thus a generally applicable method for studying the genetic and molecular associations of spatial and functional biology at single-cell resolution.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":389727,"datarank":0.9877942079057891,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.5241378399020415,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.5241378399020415,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":20,"citers_with_citation_signal":19,"citers_with_endowment":19,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1160923,"name":"Serwah Danquah","orcid":null,"position":1,"is_corresponding":false},{"id":815151,"name":"Vera Valakh","orcid":"0000-0001-7149-1562","position":2,"is_corresponding":false},{"id":6107,"name":"Brooke Simonton","orcid":"0000-0002-1366-1268","position":3,"is_corresponding":false},{"id":6106,"name":"Jon Bezney","orcid":"0000-0003-2233-4792","position":4,"is_corresponding":false},{"id":74333,"name":"Ralda Nehme","orcid":"0000-0001-7215-3311","position":5,"is_corresponding":false},{"id":6114,"name":"Brian Cleary","orcid":"0000-0003-0825-7129","position":6,"is_corresponding":false},{"id":43402,"name":"Samouil L. Farhi","orcid":"0000-0003-1359-4568","position":7,"is_corresponding":false},{"id":6115,"name":"Loïc Binan","orcid":"0000-0002-3886-5873","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:27.054415Z","pmid":"38076932","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":[]}