{"doi":"10.1101/2023.02.09.527751","title":"CPA-Perturb-seq: Multiplexed single-cell characterization of alternative polyadenylation regulators","abstract":"ABSTRACT Most mammalian genes have multiple polyA sites, representing a substantial source of transcript diversity that is governed by the cleavage and polyadenylation (CPA) regulatory machinery. To better understand how these proteins govern polyA site choice we introduce CPA-Perturb-seq, a multiplexed perturbation screen dataset of 42 known CPA regulators with a 3’ scRNA-seq readout that enables transcriptome-wide inference of polyA site usage. We develop a statistical framework to specifically identify perturbation-dependent changes in intronic and tandem polyadenylation, and discover modules of co-regulated polyA sites exhibiting distinct functional properties. By training a multi-task deep neural network (APARENT-Perturb) on our dataset, we delineate a cis -regulatory code that predicts responsiveness to perturbation and reveals interactions between distinct regulatory complexes. Finally, we leverage our framework to re-analyze published scRNA-seq datasets, identifying new regulators that affect the relative abundance of alternatively polyadenylated transcripts, and characterizing extensive cellular heterogeneity in 3’ UTR length amongst antibody-producing cells. Our work highlights the potential for multiplexed single-cell perturbation screens to further our understanding of post-transcriptional regulation in vitro and in vivo .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390928,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.865,"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":109622,"name":"Hans‐Hermann Wessels","orcid":"0000-0001-5551-404X","position":1,"is_corresponding":false},{"id":25410,"name":"Johannes Linder","orcid":"0000-0003-2134-7292","position":2,"is_corresponding":false},{"id":395344,"name":"Saket Choudhary","orcid":"0000-0001-5202-7633","position":3,"is_corresponding":false},{"id":537825,"name":"Austin Hartman","orcid":"0000-0001-7278-1852","position":4,"is_corresponding":false},{"id":164,"name":"Yuhan Hao","orcid":"0000-0002-1810-0822","position":5,"is_corresponding":false},{"id":1163193,"name":"Isabella Mascio","orcid":"0000-0003-4794-5741","position":6,"is_corresponding":false},{"id":167,"name":"Rahul Satija","orcid":"0000-0002-1479-664X","position":7,"is_corresponding":false},{"id":360,"name":"Anshul Kundaje","orcid":"0000-0003-3084-2287","position":8,"is_corresponding":false},{"id":311859,"name":"Rahul Satija","orcid":"0000-0001-9448-8833","position":9,"is_corresponding":false},{"id":721742,"name":"Madeline H. Kowalski","orcid":"0000-0002-5655-7620","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"36798324","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":[]}