{"id":"https://openalex.org/W4399722700","doi":"https://doi.org/10.1101/2024.06.15.599136","title":"Transformer-based modeling of Clonal Selection and Expression Dynamics (TraCSED) reveals resistance signatures in breast cancer","display_name":"Transformer-based modeling of Clonal Selection and Expression Dynamics (TraCSED) reveals resistance signatures in breast cancer","publication_year":2024,"publication_date":"2024-06-17","ids":{"openalex":"https://openalex.org/W4399722700","doi":"https://doi.org/10.1101/2024.06.15.599136"},"language":"en","primary_location":{"id":"doi:10.1101/2024.06.15.599136","doi":"https://doi.org/10.1101/2024.06.15.599136","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2024.06.15.599136","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2024/06/19/2024.06.15.599136.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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2024/06/19/2024.06.15.599136.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5017633078","display_name":"Nathan D Maulding","orcid":"https://orcid.org/0000-0002-8175-4538","observed_orcids":["https://orcid.org/0000-0002-8175-4538"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]},{"id":"https://openalex.org/I185103710","display_name":"University of California, Santa Cruz","ror":"https://ror.org/03s65by71","country_code":"US","type":"education","lineage":["https://openalex.org/I185103710"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nathan Maulding","raw_affiliation_strings":["University of California at Santa Cruz and Oncology Bioinformatics at Genentech"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California at Santa Cruz and Oncology Bioinformatics at Genentech","institution_ids":["https://openalex.org/I183934855","https://openalex.org/I185103710"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063274000","display_name":"Jun Zou","orcid":"https://orcid.org/0000-0001-6036-8067","observed_orcids":["https://orcid.org/0000-0001-6036-8067","https://orcid.org/0009-0008-2781-9936"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jun Zou","raw_affiliation_strings":["Discovery Oncology at Genentech"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Oncology at Genentech","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Wei Zhou","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wei Zhou","raw_affiliation_strings":["Discovery Oncology at Genentech"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Oncology at Genentech","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060142487","display_name":"Ciara Metcalfe","orcid":"https://orcid.org/0000-0001-7233-661X","observed_orcids":["https://orcid.org/0000-0001-7233-661X"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ciara Metcalfe","raw_affiliation_strings":["Discovery Oncology at Genentech"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Oncology at Genentech","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029096739","display_name":"Joshua M. Stuart","orcid":"https://orcid.org/0000-0002-2171-565X","observed_orcids":["https://orcid.org/0000-0002-2171-565X"]},"institutions":[{"id":"https://openalex.org/I185103710","display_name":"University of California, Santa Cruz","ror":"https://ror.org/03s65by71","country_code":"US","type":"education","lineage":["https://openalex.org/I185103710"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Josh Stuart","raw_affiliation_strings":["University of California at Santa Cruz"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California at Santa Cruz","institution_ids":["https://openalex.org/I185103710"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100348126","display_name":"Xin Ye","orcid":"https://orcid.org/0000-0002-8429-0900","observed_orcids":["https://orcid.org/0000-0002-8429-0900"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xin Ye","raw_affiliation_strings":["Discovery Oncology at Genentech"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Oncology at Genentech","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5018837401","display_name":"Marc A. Hafner","orcid":"https://orcid.org/0000-0003-1337-7598","observed_orcids":["https://orcid.org/0000-0003-1337-7598"]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Marc Hafner","raw_affiliation_strings":["Genentech"],"raw_orcid":"https://orcid.org/0000-0003-1337-7598","affiliations":[{"raw_affiliation_string":"Genentech","institution_ids":["https://openalex.org/I183934855"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5018837401"],"corresponding_institution_ids":["https://openalex.org/I183934855"],"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/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.9810000061988831,"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/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.9810000061988831,"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.007499999832361937,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T10183","display_name":"Breast Cancer Treatment Studies","score":0.0010000000474974513,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/clonal-selection","display_name":"clonal selection","score":0.9409999847412109},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":0.9139999747276306},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.8259999752044678},{"id":"https://openalex.org/keywords/giredestrant","display_name":"giredestrant","score":0.8169999718666077},{"id":"https://openalex.org/keywords/palbociclib","display_name":"palbociclib","score":0.9869999885559082},{"id":"https://openalex.org/keywords/estrogen-receptor","display_name":"estrogen receptor","score":0.652999997138977},{"id":"https://openalex.org/keywords/cdk4-6-inhibitors","display_name":"CDK4/6 inhibitors","score":0.9120000004768372},{"id":"https://openalex.org/keywords/single-cell-gene-expression","display_name":"single-cell gene expression","score":0.6309999823570251},{"id":"https://openalex.org/keywords/deep-learning","display_name":"deep learning","score":0.43799999356269836},{"id":"https://openalex.org/keywords/transformer","display_name":"transformer models","score":0.6159999966621399},{"id":"https://openalex.org/keywords/sncg","display_name":"SNCG","score":0.9980000257492065},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.5210000276565552},{"id":"https://openalex.org/keywords/adaptive-response","display_name":"adaptive response","score":0.3799999952316284},{"id":"https://openalex.org/keywords/transcriptional-heterogeneity","display_name":"transcriptional heterogeneity","score":0.6660000085830688}],"concepts":[{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.5943887233734131},{"id":"https://openalex.org/C81917197","wikidata":"https://www.wikidata.org/wiki/Q628760","display_name":"Selection (genetic algorithm)","level":2,"score":0.5714517831802368},{"id":"https://openalex.org/C66322947","wikidata":"https://www.wikidata.org/wiki/Q11658","display_name":"Transformer","level":3,"score":0.46034669876098633},{"id":"https://openalex.org/C90559484","wikidata":"https://www.wikidata.org/wiki/Q778379","display_name":"Expression (computer science)","level":2,"score":0.4446471929550171},{"id":"https://openalex.org/C145912823","wikidata":"https://www.wikidata.org/wiki/Q113558","display_name":"Dynamics (music)","level":2,"score":0.43697771430015564},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4133303165435791},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.393758088350296},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3918103873729706},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.36419129371643066},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.28973740339279175},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.22563615441322327},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.20426934957504272},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.12987318634986877},{"id":"https://openalex.org/C24890656","wikidata":"https://www.wikidata.org/wiki/Q82811","display_name":"Acoustics","level":1,"score":0.0867277979850769},{"id":"https://openalex.org/C119599485","wikidata":"https://www.wikidata.org/wiki/Q43035","display_name":"Electrical engineering","level":1,"score":0.0810619592666626},{"id":"https://openalex.org/C165801399","wikidata":"https://www.wikidata.org/wiki/Q25428","display_name":"Voltage","level":2,"score":0.0},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/2024.06.15.599136","doi":"https://doi.org/10.1101/2024.06.15.599136","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2024.06.15.599136","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2024/06/19/2024.06.15.599136.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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/2024.06.15.599136","doi":"https://doi.org/10.1101/2024.06.15.599136","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2024.06.15.599136","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2024/06/19/2024.06.15.599136.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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.8371999859809875,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320332193","display_name":"Genentech","ror":"https://ror.org/04gndp242"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4399722700.pdf","grobid_xml":"https://content.openalex.org/works/W4399722700.grobid-xml"},"referenced_works_count":46,"referenced_works":["https://openalex.org/W1953239809","https://openalex.org/W1987191607","https://openalex.org/W2008878539","https://openalex.org/W2054994285","https://openalex.org/W2065675729","https://openalex.org/W2102636708","https://openalex.org/W2106391833","https://openalex.org/W2129375080","https://openalex.org/W2135548733","https://openalex.org/W2138695073","https://openalex.org/W2179438025","https://openalex.org/W2186784163","https://openalex.org/W2214074259","https://openalex.org/W2344714812","https://openalex.org/W2540833380","https://openalex.org/W2557069473","https://openalex.org/W2621895366","https://openalex.org/W2767281692","https://openalex.org/W2773011778","https://openalex.org/W2806009606","https://openalex.org/W2884607428","https://openalex.org/W2902451951","https://openalex.org/W2951158909","https://openalex.org/W2951799803","https://openalex.org/W3002219094","https://openalex.org/W3015420921","https://openalex.org/W3019733875","https://openalex.org/W3043399522","https://openalex.org/W3045347505","https://openalex.org/W3045872583","https://openalex.org/W3127601051","https://openalex.org/W3130937819","https://openalex.org/W3156650572","https://openalex.org/W3157202673","https://openalex.org/W3179869469","https://openalex.org/W3187309064","https://openalex.org/W3201416000","https://openalex.org/W3211897000","https://openalex.org/W4210673686","https://openalex.org/W4255375128","https://openalex.org/W4308658133","https://openalex.org/W4309458061","https://openalex.org/W4315705290","https://openalex.org/W4317786975","https://openalex.org/W4366823165","https://openalex.org/W4384819865"],"related_works":["https://openalex.org/W4406233397","https://openalex.org/W3201416000","https://openalex.org/W3095987303","https://openalex.org/W4395958788","https://openalex.org/W4392094768","https://openalex.org/W4396919118","https://openalex.org/W1987191607","https://openalex.org/W7135350536","https://openalex.org/W3179869469","https://openalex.org/W7143441840"],"abstract_inverted_index":{"Abstract":[0],"Understanding":[1],"transcriptional":[2],"heterogeneity":[3,25],"in":[4,30,135,194],"cancer":[5],"cells":[6,86],"and":[7,20,45,61,72,96,123,158,170],"its":[8],"implication":[9],"for":[10,53],"treatment":[11,122],"response":[12,126],"is":[13,112],"critical":[14],"to":[15,85,168],"identify":[16],"how":[17],"resistance":[18,104,176],"occurs":[19],"may":[21],"be":[22,27,128],"targeted.":[23],"Such":[24],"can":[26,127],"captured":[28],"by":[29,130],"vitro":[31],"studies":[32],"through":[33],"clonal":[34,55,81],"barcoding":[35],"methods.":[36],"We":[37],"present":[38],"TraCSED":[39,67,188],"(Transformer-based":[40],"modeling":[41,54],"of":[42,64,155,165],"Clonal":[43],"Selection":[44],"Expression":[46],"Dynamics),":[47],"a":[48,100,195],"dynamic":[49],"deep":[50],"learning":[51],"approach":[52],"selection.":[56,82],"Using":[57],"single-cell":[58],"gene":[59,70],"expression":[60,154],"the":[62,73,132,136,162],"fitness":[63],"barcoded":[65],"clones,":[66],"identifies":[68],"interpretable":[69],"programs":[71],"timepoints":[74],"at":[75],"which":[76],"they":[77],"are":[78,106],"associated":[79,113,173],"with":[80,88,114,174,192],"When":[83],"applied":[84],"treated":[87],"either":[89],"giredestrant,":[90],"an":[91,178],"estrogen":[92],"receptor":[93],"(ER)":[94],"antagonist":[95],"degrader,":[97],"or":[98],"palbociclib,":[99],"CDK4/6":[101],"inhibitor,":[102],"time-dependent":[103,196],"pathways":[105,191],"revealed.":[107],"For":[108],"example,":[109],"ER":[110],"activity":[111],"positive":[115,166],"selection":[116,167],"around":[117],"day":[118],"four":[119],"under":[120],"palbociclib":[121],"this":[124],"adaptive":[125],"suppressed":[129],"combining":[131],"drugs.":[133],"Yet,":[134],"combination":[137],"treatment,":[138],"one":[139],"clone":[140],"still":[141],"emerged.":[142],"Clustering":[143],"based":[144],"on":[145],"partial":[146],"least":[147],"squares":[148],"regression":[149],"found":[150],"that":[151,180],"high":[152],"baseline":[153],"both":[156],"SNHG25":[157],"SNCG":[159],"genes":[160],"was":[161],"primary":[163],"marker":[164],"co-treatment":[169],"thus":[171],"potentially":[172],"innate":[175],"\u2013":[177],"aspect":[179],"traditional":[181],"differential":[182],"analysis":[183],"methods":[184],"missed.":[185],"In":[186],"conclusion,":[187],"enables":[189],"associating":[190],"phenotypes":[193],"manner":[197],"from":[198],"scRNA-seq":[199],"data.":[200]},"counts_by_year":[],"updated_date":"2026-10-30T12:39:25.321706","created_date":"2024-06-18T00:00:00"}