{"doi":"10.7554/elife.69571","title":"Machine learning sequence prioritization for cell type-specific enhancer design","abstract":"Recent discoveries of extreme cellular diversity in the brain warrant rapid development of technologies to access specific cell populations within heterogeneous tissue. Available approaches for engineering-targeted technologies for new neuron subtypes are low yield, involving intensive transgenic strain or virus screening. Here, we present Specific Nuclear-Anchored Independent Labeling (SNAIL), an improved virus-based strategy for cell labeling and nuclear isolation from heterogeneous tissue. SNAIL works by leveraging machine learning and other computational approaches to identify DNA sequence features that confer cell type-specific gene activation and then make a probe that drives an affinity purification-compatible reporter gene. As a proof of concept, we designed and validated two novel SNAIL probes that target parvalbumin-expressing (PV+) neurons. Nuclear isolation using SNAIL in wild-type mice is sufficient to capture characteristic open chromatin features of PV+ neurons in the cortex, striatum, and external globus pallidus. The SNAIL framework also has high utility for multispecies cell probe engineering; expression from a mouse PV+ SNAIL enhancer sequence was enriched in PV+ neurons of the macaque cortex. Expansion of this technology has broad applications in cell type-specific observation, manipulation, and therapeutics across species and disease models.","journal":"eLife","year":2022,"id":248487,"datarank":0.9922674820329771,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"self_citation_contribution":0.515098080672772,"citation_network_contribution":0.4771694013602051,"self_endowment_contribution":0.515098080672772,"citer_contribution":0.4771694013602051,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":17,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE171549","GSE63137","GSE157359","GSE161374"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":78771,"name":"Easwaran Ramamurthy","orcid":"0000-0002-2439-0600","position":1,"is_corresponding":false},{"id":78769,"name":"Ashley R. Brown","orcid":"0000-0002-3091-3930","position":2,"is_corresponding":false},{"id":826017,"name":"Naomi Shin","orcid":null,"position":3,"is_corresponding":false},{"id":367577,"name":"Yeonju Kim","orcid":"0000-0001-9220-4315","position":4,"is_corresponding":false},{"id":368276,"name":"Noelle Toong","orcid":null,"position":5,"is_corresponding":false},{"id":53198,"name":"Irene M. Kaplow","orcid":"0000-0002-8924-8269","position":6,"is_corresponding":false},{"id":323735,"name":"Morgan Wirthlin","orcid":"0000-0001-7967-7070","position":7,"is_corresponding":false},{"id":563492,"name":"Xiaoyu Zhang","orcid":"0000-0002-6617-6311","position":8,"is_corresponding":false},{"id":78772,"name":"BaDoi N. Phan","orcid":"0000-0001-6331-5980","position":9,"is_corresponding":false},{"id":367578,"name":"Grant A Fox","orcid":"0000-0002-8932-5965","position":10,"is_corresponding":false},{"id":888620,"name":"Kirsten Wade","orcid":null,"position":11,"is_corresponding":false},{"id":563356,"name":"Jing He","orcid":"0000-0001-9034-8390","position":12,"is_corresponding":false},{"id":565112,"name":"Bilge Esin Öztürk","orcid":"0000-0001-5117-077X","position":13,"is_corresponding":false},{"id":274373,"name":"Leah C. Byrne","orcid":"0000-0002-3229-4993","position":14,"is_corresponding":false},{"id":266444,"name":"William R. Stauffer","orcid":"0000-0003-1031-8824","position":15,"is_corresponding":false},{"id":307536,"name":"Kenneth N. Fish","orcid":"0000-0003-1774-3815","position":16,"is_corresponding":false},{"id":16451,"name":"Andreas R. Pfenning","orcid":"0000-0002-3447-9801","position":17,"is_corresponding":false},{"id":367576,"name":"Alyssa J. Lawler","orcid":"0000-0002-2151-5164","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T00:24:14.794521Z","pmid":"35576146","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":[]}