{"id":"https://openalex.org/W7221535488","doi":"https://doi.org/10.64898/2026.10.09.758053","title":"High-throughput variant libraries and machine learning enable robust target-site selection for toehold-switch design in Detectrons","display_name":"High-throughput variant libraries and machine learning enable robust target-site selection for toehold-switch design in Detectrons","publication_year":2026,"publication_date":"2026-10-12","ids":{"openalex":"https://openalex.org/W7221535488","doi":"https://doi.org/10.64898/2026.10.09.758053","pmid":"https://pubmed.ncbi.nlm.nih.gov/42999120","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13742442"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.09.758053","doi":"https://doi.org/10.64898/2026.10.09.758053","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.09.758053","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.09.758053.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.09.758053.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5038019961","display_name":"Jihoon Han","orcid":"https://orcid.org/0000-0001-5870-1414","observed_orcids":["https://orcid.org/0000-0001-5870-1414"]},"institutions":[{"id":"https://openalex.org/I1321430492","display_name":"Gladstone Institutes","ror":"https://ror.org/038321296","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1321430492"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jihoon Han","raw_affiliation_strings":["Gladstone Institutes;"],"raw_orcid":"https://orcid.org/0000-0001-5870-1414","affiliations":[{"raw_affiliation_string":"Gladstone Institutes;","institution_ids":["https://openalex.org/I1321430492"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5026821732","display_name":"Seth L. Shipman","orcid":"https://orcid.org/0000-0003-3130-8043","observed_orcids":["https://orcid.org/0000-0003-3130-8043"]},"institutions":[{"id":"https://openalex.org/I1321430492","display_name":"Gladstone Institutes","ror":"https://ror.org/038321296","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1321430492"]},{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Seth L Shipman","raw_affiliation_strings":["Gladstone Institutes and UCSF"],"raw_orcid":"https://orcid.org/0000-0003-3130-8043","affiliations":[{"raw_affiliation_string":"Gladstone Institutes and UCSF","institution_ids":["https://openalex.org/I1321430492","https://openalex.org/I180670191"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5026821732"],"corresponding_institution_ids":["https://openalex.org/I1321430492","https://openalex.org/I180670191"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10207","display_name":"Advanced biosensing and bioanalysis techniques","score":0.6312999725341797,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10207","display_name":"Advanced biosensing and bioanalysis techniques","score":0.6312999725341797,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.27559998631477356,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10878","display_name":"CRISPR and Genetic Engineering","score":0.01080000028014183,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/target-site-selection","display_name":"target site selection","score":0.9279999732971191},{"id":"https://openalex.org/keywords/single-nucleotide-resolution","display_name":"single-nucleotide resolution","score":0.6980000138282776},{"id":"https://openalex.org/keywords/sars-cov-2-rna-detection","display_name":"SARS-CoV-2 RNA detection","score":0.7059999704360962}],"concepts":[{"id":"https://openalex.org/C81917197","wikidata":"https://www.wikidata.org/wiki/Q628760","display_name":"Selection (genetic algorithm)","level":2,"score":0.6574000120162964},{"id":"https://openalex.org/C189430467","wikidata":"https://www.wikidata.org/wiki/Q7293293","display_name":"Ranking (information retrieval)","level":2,"score":0.6288999915122986},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.6247000098228455},{"id":"https://openalex.org/C110332635","wikidata":"https://www.wikidata.org/wiki/Q629498","display_name":"Genetic programming","level":2,"score":0.6241000294685364},{"id":"https://openalex.org/C177148314","wikidata":"https://www.wikidata.org/wiki/Q170084","display_name":"Generalization","level":2,"score":0.5681999921798706},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.5623000264167786},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.5250999927520752},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.41119998693466187},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.40959998965263367},{"id":"https://openalex.org/C19275194","wikidata":"https://www.wikidata.org/wiki/Q222903","display_name":"Multiplexing","level":2,"score":0.35740000009536743},{"id":"https://openalex.org/C51632099","wikidata":"https://www.wikidata.org/wiki/Q3985153","display_name":"Training set","level":2,"score":0.2858000099658966},{"id":"https://openalex.org/C153180895","wikidata":"https://www.wikidata.org/wiki/Q7148389","display_name":"Pattern recognition (psychology)","level":2,"score":0.2734000086784363},{"id":"https://openalex.org/C177264268","wikidata":"https://www.wikidata.org/wiki/Q1514741","display_name":"Set (abstract data type)","level":2,"score":0.2732999920845032},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.2718000113964081},{"id":"https://openalex.org/C8880873","wikidata":"https://www.wikidata.org/wiki/Q187787","display_name":"Genetic algorithm","level":2,"score":0.2597000002861023}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.64898/2026.10.09.758053","doi":"https://doi.org/10.64898/2026.10.09.758053","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.09.758053","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.09.758053.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmid:42999120","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42999120","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bioRxiv : the preprint server for biology","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.64898/2026.10.09.758053","doi":"https://doi.org/10.64898/2026.10.09.758053","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.09.758053","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.09.758053.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G148069657","display_name":"Mechanisms of non-canonical retron phage defense and expanded biotechnological applications","funder_award_id":"2509382","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320337355","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7221535488.pdf","grobid_xml":"https://content.openalex.org/works/W7221535488.grobid-xml"},"referenced_works_count":1,"referenced_works":["https://openalex.org/W7220405375"],"related_works":["https://openalex.org/W7129026930","https://openalex.org/W7220405375","https://openalex.org/W4415946648","https://openalex.org/W7129264292","https://openalex.org/W4416782249","https://openalex.org/W7139083115","https://openalex.org/W3216860704","https://openalex.org/W2120344603","https://openalex.org/W4405828828","https://openalex.org/W2996105166"],"abstract_inverted_index":{"Programmable":[0],"RNA":[1,7,54,70,145],"sensors":[2,95,125,146],"enable":[3],"sequence-specific":[4],"detection":[5],"of":[6],"inputs":[8],"for":[9,52,93,141],"diagnostics,":[10],"genetic":[11],"circuit":[12],"control,":[13],"and":[14],"multiplexed":[15],"molecular":[16],"readouts.":[17],"Although":[18],"readily":[19],"programmable,":[20],"their":[21],"performance":[22],"varies":[23],"substantially":[24],"with":[25],"the":[26,106,119],"target":[27],"site":[28],"selected":[29],"within":[30,81],"a":[31,36,47,82,138],"transcript,":[32,118],"making":[33],"target-site":[34,49,142],"selection":[35,143],"major":[37],"challenge.":[38],"Here,":[39],"we":[40,60],"report":[41],"DeSTAR":[42,136],"(Detectron":[43],"Sensor":[44],"TARget-site":[45],"ranker),":[46],"machine-learning-assisted":[48],"ranking":[50],"model":[51],"programmable":[53],"sensors.":[55],"To":[56],"train":[57],"this":[58],"model,":[59],"generated":[61],"transcript-wide,":[62],"single-nucleotide-resolution":[63],"tiling":[64],"sensor":[65,107],"libraries":[66],"across":[67,77,147],"six":[68],"diverse":[69],"targets,":[71],"enabling":[72],"generalization":[73],"to":[74],"be":[75],"tested":[76],"transcripts":[78],"rather":[79,109],"than":[80,110,130],"single":[83],"RNA.":[84],"In":[85],"leave-one-transcript-out":[86],"evaluation,":[87],"DeSTAR's":[88],"top-ranked":[89,121],"sites":[90,122],"were":[91],"enriched":[92],"high-performing":[94],"in":[96,105,144],"held-out":[97],"transcripts,":[98],"driven":[99],"predominantly":[100],"by":[101],"interpretable":[102],"sequence":[103],"grammar":[104],"stem":[108],"transcript-specific":[111],"patterns.":[112],"Prospectively,":[113],"on":[114],"an":[115],"unseen":[116],"SARS-CoV-2":[117],"model's":[120],"yielded":[123],"working":[124],"roughly":[126],"five-fold":[127],"more":[128],"often":[129],"random":[131],"selection.":[132],"These":[133],"results":[134],"support":[135],"as":[137],"generalizable":[139],"strategy":[140],"transcripts.":[148]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-10-13T00:00:00"}
