{"id":"https://openalex.org/W7225342273","doi":"https://doi.org/10.64898/2026.11.03.764017","title":"Gene regulatory architecture in antibiotic resistance is optimized for specific dynamic regimens","display_name":"Gene regulatory architecture in antibiotic resistance is optimized for specific dynamic regimens","publication_year":2026,"publication_date":"2026-11-05","ids":{"openalex":"https://openalex.org/W7225342273","doi":"https://doi.org/10.64898/2026.11.03.764017"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.03.764017","doi":"https://doi.org/10.64898/2026.11.03.764017","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.03.764017","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.03.764017.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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","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"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.03.764017.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5085218507","display_name":"Hao Geng","orcid":"https://orcid.org/0000-0001-9319-5190","observed_orcids":["https://orcid.org/0000-0001-9319-5190"]},"institutions":[{"id":"https://openalex.org/I107672454","display_name":"Dartmouth College","ror":"https://ror.org/049s0rh22","country_code":"US","type":"education","lineage":["https://openalex.org/I107672454"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hao Geng","raw_affiliation_strings":["Department of Microbiology & Immunology \u2013 Geisel School of Medicine at Dartmouth. Hanover, NH 03755, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Microbiology & Immunology \u2013 Geisel School of Medicine at Dartmouth. Hanover, NH 03755, USA","institution_ids":["https://openalex.org/I107672454"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5081501283","display_name":"Daniel Schultz","orcid":"https://orcid.org/0000-0002-3080-3416","observed_orcids":["https://orcid.org/0000-0002-3080-3416"]},"institutions":[{"id":"https://openalex.org/I107672454","display_name":"Dartmouth College","ror":"https://ror.org/049s0rh22","country_code":"US","type":"education","lineage":["https://openalex.org/I107672454"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Daniel Schultz","raw_affiliation_strings":["Department of Microbiology & Immunology \u2013 Geisel School of Medicine at Dartmouth. Hanover, NH 03755, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Microbiology & Immunology \u2013 Geisel School of Medicine at Dartmouth. Hanover, NH 03755, USA","institution_ids":["https://openalex.org/I107672454"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5081501283"],"corresponding_institution_ids":["https://openalex.org/I107672454"],"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/T10120","display_name":"Bacterial Genetics and Biotechnology","score":0.5990999937057495,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T10120","display_name":"Bacterial Genetics and Biotechnology","score":0.5990999937057495,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T11764","display_name":"Evolution and Genetic Dynamics","score":0.24269999563694,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T10621","display_name":"Gene Regulatory Network Analysis","score":0.11959999799728394,"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/antibiotic-resistance","display_name":"antibiotic resistance","score":0.9879999756813049},{"id":"https://openalex.org/keywords/gene-expression-regulation","display_name":"gene expression regulation","score":0.7609999775886536},{"id":"https://openalex.org/keywords/transcriptional-repression","display_name":"transcriptional repression","score":0.8149999976158142},{"id":"https://openalex.org/keywords/constitutive-expression","display_name":"constitutive expression","score":0.8180000185966492},{"id":"https://openalex.org/keywords/cost-function","display_name":"cost function","score":0.40700000524520874},{"id":"https://openalex.org/keywords/stochastic-gene-expression","display_name":"stochastic gene expression","score":0.6150000095367432}],"concepts":[{"id":"https://openalex.org/C158448853","wikidata":"https://www.wikidata.org/wiki/Q425218","display_name":"Repressor","level":4,"score":0.8841000199317932},{"id":"https://openalex.org/C186310378","wikidata":"https://www.wikidata.org/wiki/Q941796","display_name":"Psychological repression","level":4,"score":0.829800009727478},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.623199999332428},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5900999903678894},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.5444999933242798},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.5209000110626221},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.5083000063896179},{"id":"https://openalex.org/C114851261","wikidata":"https://www.wikidata.org/wiki/Q12147416","display_name":"Drug resistance","level":2,"score":0.503000020980835},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4332999885082245},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.4124999940395355},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.3873000144958496},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3817000091075897},{"id":"https://openalex.org/C27153228","wikidata":"https://www.wikidata.org/wiki/Q3787274","display_name":"Transcriptional regulation","level":4,"score":0.3709000051021576},{"id":"https://openalex.org/C33498276","wikidata":"https://www.wikidata.org/wiki/Q2138797","display_name":"Regulator gene","level":4,"score":0.3544999957084656},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.335099995136261},{"id":"https://openalex.org/C501593827","wikidata":"https://www.wikidata.org/wiki/Q12187","display_name":"Antibiotics","level":2,"score":0.3037000000476837},{"id":"https://openalex.org/C21592294","wikidata":"https://www.wikidata.org/wiki/Q3238407","display_name":"Regulatory sequence","level":4,"score":0.2919999957084656},{"id":"https://openalex.org/C94665300","wikidata":"https://www.wikidata.org/wiki/Q63391344","display_name":"Antibiotic resistance","level":3,"score":0.287200003862381},{"id":"https://openalex.org/C90559484","wikidata":"https://www.wikidata.org/wiki/Q778379","display_name":"Expression (computer science)","level":2,"score":0.2635999917984009},{"id":"https://openalex.org/C2775930736","wikidata":"https://www.wikidata.org/wiki/Q7309708","display_name":"Regulatory state","level":3,"score":0.25999999046325684},{"id":"https://openalex.org/C101762097","wikidata":"https://www.wikidata.org/wiki/Q224093","display_name":"Promoter","level":4,"score":0.25290000438690186},{"id":"https://openalex.org/C179926584","wikidata":"https://www.wikidata.org/wiki/Q207714","display_name":"Transcription (linguistics)","level":2,"score":0.25279998779296875},{"id":"https://openalex.org/C2780852648","wikidata":"https://www.wikidata.org/wiki/Q143584","display_name":"SOS response","level":4,"score":0.25209999084472656}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.03.764017","doi":"https://doi.org/10.64898/2026.11.03.764017","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.03.764017","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.03.764017.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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.03.764017","doi":"https://doi.org/10.64898/2026.11.03.764017","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.03.764017","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.03.764017.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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","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/G2412074246","display_name":"Emergence of Heterogeneity in Bacteria During Antibiotic Responses","funder_award_id":"2412766","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G6821688019","display_name":"eMB: Data-driven prediction of phenotypic heterogeneity: from single-cells to populations","funder_award_id":"2527337","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G8604894762","display_name":null,"funder_award_id":"DE-SC0026232","funder_id":"https://openalex.org/F4320306084","funder_display_name":"U.S. Department of Energy"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320306084","display_name":"U.S. Department of Energy","ror":"https://ror.org/01bj3aw27"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225342273.pdf","grobid_xml":"https://content.openalex.org/works/W7225342273.grobid-xml"},"referenced_works_count":76,"referenced_works":["https://openalex.org/W154073066","https://openalex.org/W1507498672","https://openalex.org/W1529365648","https://openalex.org/W1553861224","https://openalex.org/W1590222219","https://openalex.org/W1832966438","https://openalex.org/W1897512913","https://openalex.org/W1961858939","https://openalex.org/W1970912575","https://openalex.org/W1972412013","https://openalex.org/W1973943921","https://openalex.org/W1976971043","https://openalex.org/W1981267913","https://openalex.org/W1985032743","https://openalex.org/W1985161570","https://openalex.org/W1986772002","https://openalex.org/W1993482839","https://openalex.org/W2001963002","https://openalex.org/W2012977051","https://openalex.org/W2015756528","https://openalex.org/W2018435536","https://openalex.org/W2019460535","https://openalex.org/W2028553878","https://openalex.org/W2028979517","https://openalex.org/W2035018687","https://openalex.org/W2038701138","https://openalex.org/W2043487490","https://openalex.org/W2046451925","https://openalex.org/W2053240640","https://openalex.org/W2053272135","https://openalex.org/W2061659241","https://openalex.org/W2063558597","https://openalex.org/W2068872007","https://openalex.org/W2091198609","https://openalex.org/W2097842145","https://openalex.org/W2111354165","https://openalex.org/W2113790776","https://openalex.org/W2114561860","https://openalex.org/W2115606218","https://openalex.org/W2118464978","https://openalex.org/W2123505432","https://openalex.org/W2126998351","https://openalex.org/W2131081634","https://openalex.org/W2131256712","https://openalex.org/W2134150890","https://openalex.org/W2136569555","https://openalex.org/W2139500219","https://openalex.org/W2140347764","https://openalex.org/W2142182986","https://openalex.org/W2152195021","https://openalex.org/W2153209413","https://openalex.org/W2154881669","https://openalex.org/W2156533749","https://openalex.org/W2156781574","https://openalex.org/W2159356885","https://openalex.org/W2159579053","https://openalex.org/W2161975040","https://openalex.org/W2171280873","https://openalex.org/W2171535756","https://openalex.org/W2182611834","https://openalex.org/W2253216140","https://openalex.org/W2262666557","https://openalex.org/W2543218903","https://openalex.org/W2571367575","https://openalex.org/W2588008367","https://openalex.org/W2591398936","https://openalex.org/W2606611438","https://openalex.org/W2758091881","https://openalex.org/W2762262959","https://openalex.org/W2766736626","https://openalex.org/W2784779095","https://openalex.org/W3004703159","https://openalex.org/W3108851848","https://openalex.org/W4297141455","https://openalex.org/W4392185815","https://openalex.org/W4410267490"],"related_works":["https://openalex.org/W4297141455","https://openalex.org/W2766736626","https://openalex.org/W4410267490","https://openalex.org/W4392185815","https://openalex.org/W2888840473","https://openalex.org/W7223091658","https://openalex.org/W2970335770","https://openalex.org/W4224952696","https://openalex.org/W4404916999","https://openalex.org/W2287149765"],"abstract_inverted_index":{"Abstract":[0],"Cellular":[1],"responses":[2,39,307,333],"to":[3,15,116,262,271,278,293,310,321,334,419],"antibiotics":[4],"face":[5],"a":[6,93,97,102,112,130,173,180,202,269,328],"fundamental":[7],"trade-off:":[8],"resistance":[9,27,47,113,246,291,299,408],"must":[10,216],"be":[11,314],"deployed":[12],"quickly":[13],"enough":[14],"prevent":[16],"the":[17,22,32,35,65,80,106,117,120,135,140,143,146,154,208,214,232,257,260,263,287,295,348,358,363,367,377,387,390,400,411],"accumulation":[18],"of":[19,26,34,69,82,96,111,119,145,153,164,169,192,196,207,223,231,245,259,265,289,297,331,355,360,369,386,392,402,414],"drug":[20,83,107,121,187,323,370,394],"inside":[21],"cell,":[23],"but":[24,50],"expression":[25,110,168,191,198,288,354,382],"genes":[28,292],"is":[29,48,75,210,302],"costly":[30],"in":[31,150,238,380,406,416],"absence":[33],"drug.":[36],"Therefore,":[37],"antibiotic":[38,99,290,332,420],"are":[40,62,276,318,339],"typically":[41],"regulated,":[42],"controlling":[43],"not":[44,77,303],"only":[45,212],"whether":[46],"expressed,":[49],"also":[51,220],"when,":[52],"how":[53,57,79],"strongly,":[54],"and":[55,67,71,108,125,148,177,205,249,352,357,372,410],"for":[56,86,161],"long.":[58],"These":[59,396],"regulatory":[60,88,155,274,337,403],"strategies":[61,275,338],"implemented":[63],"through":[64],"strength":[66],"arrangement":[68],"promoters":[70],"operators.":[72],"However,":[73,305],"it":[74,301],"still":[76],"clear":[78],"dynamics":[81,258,368],"exposure":[84,248,371],"select":[85],"specific":[87,281],"strategies.":[89],"Here,":[90,325],"we":[91,326],"develop":[92],"dynamical":[94],"model":[95,330],"typical":[98],"response,":[100,147],"where":[101],"transcriptional":[103],"repressor":[104,209,233,239,388],"senses":[105],"regulates":[109],"protein,":[114],"coupled":[115],"effects":[118],"on":[122,139,366,373],"cell":[123,141],"growth":[124],"gene":[126,266,381],"expression.":[127],"We":[128,183,345],"define":[129],"cost":[131],"function":[132],"that":[133,185,229,347],"weighs":[134],"different":[136,158,342],"burdens":[137],"imposed":[138],"over":[142],"course":[144],"perform":[149],"silico":[151],"optimization":[152],"parameters":[156],"under":[157,280,341],"selective":[159,282,343],"pressures":[160],"three":[162],"architectures":[163,404],"increasing":[165],"complexity:":[166],"constitutive":[167,190,203,351],"resistance,":[170,193,356],"repression":[171,178,200],"by":[172,179,201,362],"constitutively":[174],"expressed":[175],"repressor,":[176,204,364],"self-regulated":[181],"repressor.":[182],"find":[184],"strong":[186],"exposures":[188],"favor":[189,199],"high":[194],"costs":[195,296,375],"basal":[197],"self-regulation":[206,230,361,385],"favored":[211],"when":[213,300,316],"response":[215],"provide":[217],"protection":[218],"while":[219],"restraining":[221],"overexpression":[222],"resistance.":[224],"Stochastic":[225],"simulations":[226],"further":[227,383],"show":[228,346],"protects":[234],"cells":[235,317],"against":[236],"fluctuations":[237],"levels,":[240],"which":[241,273,312,336,374],"cause":[242],"unnecessary":[243],"induction":[244,251],"before":[247],"failed":[250],"after":[252],"exposure.":[253],"This":[254],"framework":[255],"links":[256],"environment":[261],"evolution":[264],"regulation,":[267],"providing":[268],"basis":[270],"predict":[272],"expected":[277],"arise":[279],"pressures.":[283,344],"Significance":[284],"Bacteria":[285],"regulate":[286],"avoid":[294],"producing":[298],"needed.":[304],"regulated":[306,353],"take":[308],"time":[309],"activate,":[311],"can":[313],"fatal":[315],"suddenly":[319],"exposed":[320,418],"large":[322],"doses.":[324],"use":[327,359],"mathematical":[329],"identify":[335],"optimal":[340],"choice":[349],"between":[350],"depend":[365],"dominate":[376],"response.":[378],"Noise":[379],"favors":[384],"near":[389],"limit":[391],"tolerable":[393],"exposures.":[395],"results":[397],"help":[398],"explain":[399],"diversity":[401],"found":[405],"natural":[407],"mechanisms,":[409],"frequent":[412],"loss":[413],"regulation":[415],"pathogens":[417],"treatments.":[421]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-06T00:00:00"}
