{"doi":"10.1016/j.molcel.2023.11.021","title":"High-throughput PRIME-editing screens identify functional DNA variants in the human genome","abstract":"Despite tremendous progress in detecting DNA variants associated with human disease, interpreting their functional impact in a high-throughput and single-base resolution manner remains challenging. Here, we develop a pooled prime-editing screen method, PRIME, that can be applied to characterize thousands of coding and non-coding variants in a single experiment with high reproducibility. To showcase its applications, we first identified essential nucleotides for a 716 bp MYC enhancer via PRIME-mediated single-base resolution analysis. Next, we applied PRIME to functionally characterize 1,304 genome-wide association study (GWAS)-identified non-coding variants associated with breast cancer and 3,699 variants from ClinVar. We discovered that 103 non-coding variants and 156 variants of uncertain significance are functional via affecting cell fitness. Collectively, we demonstrate that PRIME is capable of characterizing genetic variants at single-base resolution and scale, advancing accurate genome annotation for disease risk prediction, diagnosis, and therapeutic target identification.","journal":"Molecular Cell","year":2023,"id":318261,"datarank":1.6802095356791045,"base_score":4.219507705176107,"endowment":4.219507705176107,"self_citation_contribution":0.6329261557764161,"citation_network_contribution":1.0472833799026884,"self_endowment_contribution":0.6329261557764161,"citer_contribution":1.0472833799026884,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":66,"citers_with_citation_signal":52,"citers_with_endowment":52,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":true,"deposit_databanks":{"SRA":["PRJNA909251"],"BioProject":["PRJNA909251"]},"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":65843,"name":"Han Yang","orcid":"0000-0002-9150-8146","position":1,"is_corresponding":false},{"id":339081,"name":"Jovia L. Nierenberg","orcid":"0000-0003-2376-6714","position":2,"is_corresponding":false},{"id":1025344,"name":"Yifan Sun","orcid":"0000-0002-1409-6520","position":3,"is_corresponding":false},{"id":555502,"name":"Jiawen Chen","orcid":"0009-0003-6582-6559","position":4,"is_corresponding":false},{"id":1025345,"name":"Cooper Beaman","orcid":"0000-0003-0933-5504","position":5,"is_corresponding":false},{"id":1025346,"name":"Thu Huong Pham","orcid":"0000-0002-1615-8916","position":6,"is_corresponding":false},{"id":1026096,"name":"Mai Nobuhara","orcid":null,"position":7,"is_corresponding":false},{"id":700562,"name":"Maya Asami Takagi","orcid":"0000-0003-0032-1130","position":8,"is_corresponding":false},{"id":1025347,"name":"Vivek Narayan","orcid":"0000-0002-3232-7898","position":9,"is_corresponding":false},{"id":24805,"name":"Yun Li","orcid":"0000-0002-9275-4189","position":10,"is_corresponding":false},{"id":52036,"name":"Elad Ziv","orcid":"0000-0002-2324-2884","position":11,"is_corresponding":false},{"id":29911,"name":"Yin Shen","orcid":"0000-0001-9901-5613","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:07:01.300821Z","pmid":"38134886","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":[]}