{"id":"https://openalex.org/W4386945231","doi":"https://doi.org/10.7554/elife.85023","title":"Diverse evolutionary pathways challenge the use of collateral sensitivity as a strategy to suppress resistance","display_name":"Diverse evolutionary pathways challenge the use of collateral sensitivity as a strategy to suppress resistance","publication_year":2023,"publication_date":"2023-09-22","ids":{"openalex":"https://openalex.org/W4386945231","doi":"https://doi.org/10.7554/elife.85023","pmid":"https://pubmed.ncbi.nlm.nih.gov/37737220","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/10695565"},"language":"en","primary_location":{"id":"doi:10.7554/elife.85023","doi":"https://doi.org/10.7554/elife.85023","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.85023","pdf_url":"https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvODUwMjMvZWxpZmUtODUwMjMtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzg1MDIz/elife-85023-v1.pdf?_hash=xEUFpzsUmxbQ4dgyVtpDMXg%2F%2FMaaFQAQbZeDBIMO9TE%3D","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvODUwMjMvZWxpZmUtODUwMjMtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzg1MDIz/elife-85023-v1.pdf?_hash=xEUFpzsUmxbQ4dgyVtpDMXg%2F%2FMaaFQAQbZeDBIMO9TE%3D","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5038120209","display_name":"Rebecca E. K. Mandt","orcid":"https://orcid.org/0000-0001-7165-7876","observed_orcids":["https://orcid.org/0000-0001-7165-7876"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rebecca E.K. Mandt","raw_affiliation_strings":["Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5035010935","display_name":"Madeline R. Luth","orcid":"https://orcid.org/0000-0001-9059-1200","observed_orcids":["https://orcid.org/0000-0001-9059-1200"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Madeline R. Luth","raw_affiliation_strings":["Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, United States","Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California, San Diego"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, United States","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California, San Diego","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5078323744","display_name":"Mark A. Tye","orcid":"https://orcid.org/0000-0002-9456-0767","observed_orcids":["https://orcid.org/0000-0002-9456-0767"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I4210155419","display_name":"Center for Systems Biology","ror":"https://ror.org/05r3dyn47","country_code":"US","type":"facility","lineage":["https://openalex.org/I136199984","https://openalex.org/I4210087915","https://openalex.org/I4210155419","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mark A. Tye","raw_affiliation_strings":["Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, United States","Harvard Graduate School of Arts and Sciences, Cambridge, MA 02138, United States","Center for Systems Biology, Massachusetts General Hospital; Harvard Graduate School of Arts and Sciences","Harvard Graduate School of Arts and Sciences"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, United States","institution_ids":["https://openalex.org/I4210087915","https://openalex.org/I4210155419"]},{"raw_affiliation_string":"Harvard Graduate School of Arts and Sciences, Cambridge, MA 02138, United States","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Center for Systems Biology, Massachusetts General Hospital; Harvard Graduate School of Arts and Sciences","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915","https://openalex.org/I4210155419"]},{"raw_affiliation_string":"Harvard Graduate School of Arts and Sciences","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067096193","display_name":"Ralph Mazitschek","orcid":"https://orcid.org/0000-0002-1105-689X","observed_orcids":["https://orcid.org/0000-0002-1105-689X"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I4210155419","display_name":"Center for Systems Biology","ror":"https://ror.org/05r3dyn47","country_code":"US","type":"facility","lineage":["https://openalex.org/I136199984","https://openalex.org/I4210087915","https://openalex.org/I4210155419","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ralph Mazitschek","raw_affiliation_strings":["Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, United States","Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","Center for Systems Biology, Massachusetts General Hospital","Center for Systems Biology, Massachusetts General Hospital; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, United States","institution_ids":["https://openalex.org/I4210087915","https://openalex.org/I4210155419"]},{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Center for Systems Biology, Massachusetts General Hospital","institution_ids":["https://openalex.org/I4210087915","https://openalex.org/I4210155419"]},{"raw_affiliation_string":"Center for Systems Biology, Massachusetts General Hospital; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915","https://openalex.org/I4210155419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002312589","display_name":"Sabine Ottilie","orcid":"https://orcid.org/0000-0001-9797-2612","observed_orcids":["https://orcid.org/0000-0001-9797-2612"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sabine Ottilie","raw_affiliation_strings":["Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, United States","Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California, San Diego"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, United States","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California, San Diego","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080934184","display_name":"Elizabeth A. Winzeler","orcid":"https://orcid.org/0000-0002-4049-2113","observed_orcids":["https://orcid.org/0000-0002-4049-2113"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Elizabeth A. Winzeler","raw_affiliation_strings":["Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, United States","Skaggs School of Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States","Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California, San Diego; Skaggs School of Pharmaceutical Sciences, University of California, San Diego","Skaggs School of Pharmaceutical Sciences, University of California, San Diego"],"raw_orcid":"https://orcid.org/0000-0002-4049-2113","affiliations":[{"raw_affiliation_string":"Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, United States","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Skaggs School of Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, University of California, San Diego; Skaggs School of Pharmaceutical Sciences, University of California, San Diego","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Skaggs School of Pharmaceutical Sciences, University of California, San Diego","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003297972","display_name":"Mar\u00eda Jos\u00e9 Lafuente-Monasterio","orcid":"https://orcid.org/0000-0002-4583-9649","observed_orcids":["https://orcid.org/0000-0002-4583-9649"]},"institutions":[{"id":"https://openalex.org/I4210151147","display_name":"GlaxoSmithKline (Spain)","ror":"https://ror.org/049nnjd96","country_code":"ES","type":"company","lineage":["https://openalex.org/I188950975","https://openalex.org/I4210151147"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Maria Jose Lafuente-Monasterio","raw_affiliation_strings":["Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain","Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain","institution_ids":["https://openalex.org/I4210151147"]},{"raw_affiliation_string":"Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003484208","display_name":"Francisco\u2010Javier Gamo","orcid":"https://orcid.org/0000-0002-1854-2882","observed_orcids":["https://orcid.org/0000-0002-1854-2882"]},"institutions":[{"id":"https://openalex.org/I4210151147","display_name":"GlaxoSmithKline (Spain)","ror":"https://ror.org/049nnjd96","country_code":"ES","type":"company","lineage":["https://openalex.org/I188950975","https://openalex.org/I4210151147"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Francisco Javier Gamo","raw_affiliation_strings":["Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain","Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain","institution_ids":["https://openalex.org/I4210151147"]},{"raw_affiliation_string":"Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmithKline","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011964221","display_name":"Dyann F. Wirth","orcid":"https://orcid.org/0000-0002-8604-4455","observed_orcids":["https://orcid.org/0000-0002-8604-4455"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dyann F. Wirth","raw_affiliation_strings":["Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","Infectious Disease and Microbiome Program, The Broad Institute, Cambridge, Massachusetts, 02142, United States","Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health; Infectious Disease and Microbiome Program, The Broad Institute","Infectious Disease and Microbiome Program, The Broad Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Infectious Disease and Microbiome Program, The Broad Institute, Cambridge, Massachusetts, 02142, United States","institution_ids":["https://openalex.org/I107606265"]},{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health; Infectious Disease and Microbiome Program, The Broad Institute","institution_ids":["https://openalex.org/I107606265","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Infectious Disease and Microbiome Program, The Broad Institute","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5081926124","display_name":"Amanda K. Lukens","orcid":"https://orcid.org/0000-0002-9560-7643","observed_orcids":["https://orcid.org/0000-0002-9560-7643"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Amanda K. Lukens","raw_affiliation_strings":["Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","Infectious Disease and Microbiome Program, The Broad Institute, Cambridge, Massachusetts, 02142, United States","Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health; Infectious Disease and Microbiome Program, The Broad Institute","Infectious Disease and Microbiome Program, The Broad Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Infectious Disease and Microbiome Program, The Broad Institute, Cambridge, Massachusetts, 02142, United States","institution_ids":["https://openalex.org/I107606265"]},{"raw_affiliation_string":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health; Infectious Disease and Microbiome Program, The Broad Institute","institution_ids":["https://openalex.org/I107606265","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Infectious Disease and Microbiome Program, The Broad Institute","institution_ids":["https://openalex.org/I107606265"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":6,"corresponding_author_ids":["https://openalex.org/A5081926124"],"corresponding_institution_ids":["https://openalex.org/I107606265","https://openalex.org/I136199984"],"apc_list":{"value":3000,"currency":"USD","value_usd":2500},"apc_paid":{"value":2829,"currency":"EUR","value_usd":3051},"fwci":1.3981,"has_fulltext":true,"cited_by_count":6,"citation_normalized_percentile":{"value":0.79998268,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":93,"max":97},"biblio":{"volume":"12","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10091","display_name":"Malaria Research and Control","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10091","display_name":"Malaria Research and Control","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11764","display_name":"Evolution and Genetic Dynamics","score":0.00019999999494757503,"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/T11075","display_name":"Insect Resistance and Genetics","score":9.999999747378752e-05,"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/collateral-sensitivity","display_name":"collateral sensitivity","score":0.9850000143051147},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.6759999990463257},{"id":"https://openalex.org/keywords/malaria","display_name":"malaria","score":0.7829999923706055},{"id":"https://openalex.org/keywords/plasmodium-falciparum","display_name":"Plasmodium falciparum","score":0.9710000157356262},{"id":"https://openalex.org/keywords/dihydroorotate-dehydrogenase","display_name":"dihydroorotate dehydrogenase","score":0.9789999723434448},{"id":"https://openalex.org/keywords/dhodh-inhibitors","display_name":"DHODH inhibitors","score":0.9440000057220459},{"id":"https://openalex.org/keywords/cross-resistance","display_name":"cross-resistance","score":0.9409999847412109},{"id":"https://openalex.org/keywords/copy-number-variation","display_name":"copy number variation","score":0.8600000143051147},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.492000013589859},{"id":"https://openalex.org/keywords/resistance-suppression","display_name":"resistance suppression","score":0.5989999771118164}],"concepts":[{"id":"https://openalex.org/C21200559","wikidata":"https://www.wikidata.org/wiki/Q7451068","display_name":"Sensitivity (control systems)","level":2,"score":0.5356281399726868},{"id":"https://openalex.org/C2993632694","wikidata":"https://www.wikidata.org/wiki/Q45939","display_name":"Collateral damage","level":2,"score":0.5266687273979187},{"id":"https://openalex.org/C57473165","wikidata":"https://www.wikidata.org/wiki/Q7315604","display_name":"Resistance (ecology)","level":2,"score":0.5199010372161865},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.47964268922805786},{"id":"https://openalex.org/C2777910564","wikidata":"https://www.wikidata.org/wiki/Q694563","display_name":"Collateral","level":2,"score":0.47655561566352844},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4199443459510803},{"id":"https://openalex.org/C78458016","wikidata":"https://www.wikidata.org/wiki/Q840400","display_name":"Evolutionary biology","level":1,"score":0.37048226594924927},{"id":"https://openalex.org/C144133560","wikidata":"https://www.wikidata.org/wiki/Q4830453","display_name":"Business","level":0,"score":0.20512664318084717},{"id":"https://openalex.org/C18903297","wikidata":"https://www.wikidata.org/wiki/Q7150","display_name":"Ecology","level":1,"score":0.1701030433177948},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.12751495838165283},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.12190094590187073},{"id":"https://openalex.org/C73484699","wikidata":"https://www.wikidata.org/wiki/Q161733","display_name":"Criminology","level":1,"score":0.0},{"id":"https://openalex.org/C24326235","wikidata":"https://www.wikidata.org/wiki/Q126095","display_name":"Electronic engineering","level":1,"score":0.0},{"id":"https://openalex.org/C10138342","wikidata":"https://www.wikidata.org/wiki/Q43015","display_name":"Finance","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000081164","descriptor_name":"Drug Collateral Sensitivity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000090722","descriptor_name":"Dihydroorotate Dehydrogenase","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000962","descriptor_name":"Antimalarials","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000962","descriptor_name":"Antimalarials","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010271","descriptor_name":"Parasites","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D010963","descriptor_name":"Plasmodium falciparum","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016778","descriptor_name":"Malaria, Falciparum","qualifier_ui":"Q000469","qualifier_name":"parasitology","is_major_topic":true},{"descriptor_ui":"D044925","descriptor_name":"Oxidoreductases Acting on CH-CH Group Donors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D044925","descriptor_name":"Oxidoreductases Acting on CH-CH Group Donors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D056915","descriptor_name":"DNA Copy Number Variations","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":6,"locations":[{"id":"doi:10.7554/elife.85023","doi":"https://doi.org/10.7554/elife.85023","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.85023","pdf_url":"https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvODUwMjMvZWxpZmUtODUwMjMtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzg1MDIz/elife-85023-v1.pdf?_hash=xEUFpzsUmxbQ4dgyVtpDMXg%2F%2FMaaFQAQbZeDBIMO9TE%3D","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},{"id":"doi:10.1101/2022.04.07.486819","doi":"https://doi.org/10.1101/2022.04.07.486819","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.04.07.486819","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/07/2022.04.07.486819.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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmh:oai:pubmedcentral.nih.gov:10695565","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10695565","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10695565/pdf/elife-85023.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"Text"},{"id":"pmid:37737220","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37737220","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":"eLife","raw_type":"Journal Article"},{"id":"pmh:oai:escholarship.org:ark:/13030/qt97g122x3","doi":null,"is_oa":true,"landing_page_url":"https://escholarship.org/uc/item/97g122x3","pdf_url":"https://escholarship.org/content/qt97g122x3/qt97g122x3.pdf","source":{"id":"https://openalex.org/S4306400115","display_name":"eScholarship (California Digital Library)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2801248553","host_organization_name":"California Digital Library","host_organization_lineage":["https://openalex.org/I2801248553"],"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":"eLife, vol 12","raw_type":"article"},{"id":"pmh:oai:doaj.org/article:0401791b59174b2ea135e6bcfac22ca9","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/0401791b59174b2ea135e6bcfac22ca9","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"eLife, Vol 12 (2023)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.7554/elife.85023","doi":"https://doi.org/10.7554/elife.85023","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.85023","pdf_url":"https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvODUwMjMvZWxpZmUtODUwMjMtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzg1MDIz/elife-85023-v1.pdf?_hash=xEUFpzsUmxbQ4dgyVtpDMXg%2F%2FMaaFQAQbZeDBIMO9TE%3D","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.8371999859809875}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1275747955","display_name":null,"funder_award_id":"T32 GM008666","funder_id":"https://openalex.org/F4320332603","funder_display_name":"University of California, San Diego"},{"id":"https://openalex.org/G1384877631","display_name":null,"funder_award_id":"S10 OD026929","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G1476237564","display_name":null,"funder_award_id":"#S10 OD026929","funder_id":"https://openalex.org/F4320332603","funder_display_name":"University of California, San Diego"},{"id":"https://openalex.org/G1547284777","display_name":null,"funder_award_id":"GM008666","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G1947521700","display_name":"Targeting the Mitochondrion of P. falciparum","funder_award_id":"R01AI093716","funder_id":"https://openalex.org/F4320337355","funder_display_name":"National Institute of Allergy and Infectious Diseases"},{"id":"https://openalex.org/G2387613229","display_name":null,"funder_award_id":"GM008666","funder_id":"https://openalex.org/F4320332603","funder_display_name":"University of California, San Diego"},{"id":"https://openalex.org/G3306396600","display_name":"Illumina NovaSeq 6000 Sequencing System","funder_award_id":"1s10od026929-01","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G3549828030","display_name":null,"funder_award_id":"NIH T32","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G4523881014","display_name":null,"funder_award_id":"T32 grant","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G5918143493","display_name":null,"funder_award_id":"OPP1132451","funder_id":"https://openalex.org/F4320306137","funder_display_name":"Bill and Melinda Gates Foundation"},{"id":"https://openalex.org/G6154561313","display_name":null,"funder_award_id":"T32 GM008666","funder_id":"https://openalex.org/F4320322413","funder_display_name":"Medicines for Malaria Venture"},{"id":"https://openalex.org/G6917180116","display_name":"Training Program in Basic and Clinical Genetics","funder_award_id":"T32GM008666","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G9000858489","display_name":"Defining the resistome in P. falciparum: evolution and mechanism","funder_award_id":"R01AI169892","funder_id":"https://openalex.org/F4320337355","funder_display_name":"National Institute of Allergy and Infectious Diseases"}],"funders":[{"id":"https://openalex.org/F4320306137","display_name":"Bill and Melinda Gates Foundation","ror":"https://ror.org/0456r8d26"},{"id":"https://openalex.org/F4320310169","display_name":"University of Texas Southwestern Medical Center","ror":"https://ror.org/05byvp690"},{"id":"https://openalex.org/F4320310609","display_name":"Harvard T.H. Chan School of Public Health","ror":"https://ror.org/03vek6s52"},{"id":"https://openalex.org/F4320322413","display_name":"Medicines for Malaria Venture","ror":"https://ror.org/00p9jf779"},{"id":"https://openalex.org/F4320327703","display_name":"ExxonMobil Foundation","ror":null},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320332603","display_name":"University of California, San Diego","ror":"https://ror.org/0168r3w48"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"},{"id":"https://openalex.org/F4320337355","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4386945231.pdf","grobid_xml":"https://content.openalex.org/works/W4386945231.grobid-xml"},"referenced_works_count":71,"referenced_works":["https://openalex.org/W360939430","https://openalex.org/W1862162596","https://openalex.org/W1976977157","https://openalex.org/W1977195114","https://openalex.org/W1977845940","https://openalex.org/W1983042430","https://openalex.org/W1995421796","https://openalex.org/W1996323490","https://openalex.org/W1996682530","https://openalex.org/W2015791647","https://openalex.org/W2020251171","https://openalex.org/W2024417676","https://openalex.org/W2028918918","https://openalex.org/W2030481162","https://openalex.org/W2045618634","https://openalex.org/W2055958358","https://openalex.org/W2063538123","https://openalex.org/W2064023213","https://openalex.org/W2080777238","https://openalex.org/W2088791835","https://openalex.org/W2107676192","https://openalex.org/W2108545589","https://openalex.org/W2110269548","https://openalex.org/W2111020219","https://openalex.org/W2114818342","https://openalex.org/W2134089325","https://openalex.org/W2137393196","https://openalex.org/W2146619735","https://openalex.org/W2146694756","https://openalex.org/W2150670359","https://openalex.org/W2152297499","https://openalex.org/W2153077121","https://openalex.org/W2159444797","https://openalex.org/W2164103310","https://openalex.org/W2169023801","https://openalex.org/W2222642144","https://openalex.org/W2294346154","https://openalex.org/W2315025523","https://openalex.org/W2497068279","https://openalex.org/W2527582579","https://openalex.org/W2536267708","https://openalex.org/W2553103457","https://openalex.org/W2557523555","https://openalex.org/W2576072275","https://openalex.org/W2595618202","https://openalex.org/W2598900197","https://openalex.org/W2602169678","https://openalex.org/W2603629512","https://openalex.org/W2743325497","https://openalex.org/W2773291920","https://openalex.org/W2783969665","https://openalex.org/W2784798198","https://openalex.org/W2808371897","https://openalex.org/W2810656554","https://openalex.org/W2888220409","https://openalex.org/W2898696707","https://openalex.org/W2908913542","https://openalex.org/W2911287327","https://openalex.org/W2914921463","https://openalex.org/W2944077394","https://openalex.org/W2948255001","https://openalex.org/W2951273658","https://openalex.org/W2963818102","https://openalex.org/W2982049202","https://openalex.org/W2982357988","https://openalex.org/W2982472703","https://openalex.org/W2992612503","https://openalex.org/W2995437536","https://openalex.org/W3009760483","https://openalex.org/W3162929352","https://openalex.org/W4210262416"],"related_works":["https://openalex.org/W2783969665","https://openalex.org/W3216757389","https://openalex.org/W2015791647","https://openalex.org/W2150670359","https://openalex.org/W2146619735","https://openalex.org/W2898696707","https://openalex.org/W2557587313","https://openalex.org/W1991103744","https://openalex.org/W2018593882","https://openalex.org/W2146694756"],"abstract_inverted_index":{"Abstract":[0],"Drug":[1,24],"resistance":[2,31,54,169],"remains":[3],"a":[4,87,191],"major":[5],"obstacle":[6],"to":[7,20,32,38,49,86,147,153,164,180,198],"malaria":[8],"control":[9],"and":[10,77,149,183,201],"eradication":[11],"efforts,":[12],"necessitating":[13],"the":[14,39,51,68,75,108,117,126,137,166,171,206,221,225],"development":[15],"of":[16,53,81,90,125,168,173,214,224],"novel":[17],"therapeutic":[18],"strategies":[19],"treat":[21],"this":[22,59],"disease.":[23],"combinations":[25],"based":[26],"on":[27,95],"collateral":[28,63,78,159],"sensitivity,":[29],"wherein":[30],"one":[33,96],"drug":[34],"causes":[35],"increased":[36],"sensitivity":[37,64,79,146,160],"partner":[40],"drug,":[41],"have":[42],"been":[43],"proposed":[44],"as":[45,203,205],"an":[46],"evolutionary":[47],"strategy":[48],"suppress":[50,165],"emergence":[52,167,213],"in":[55,114,136,170,209],"pathogen":[56],"populations.":[57],"In":[58],"study,":[60],"we":[61,156],"explore":[62],"between":[65],"compounds":[66,200],"targeting":[67],"Plasmodium":[69],"dihydroorotate":[70],"dehydrogenase":[71],"(DHODH).":[72],"We":[73,93,121],"profiled":[74],"cross-resistance":[76],"phenotypes":[80],"several":[82],"DHODH":[83,91,109,127,192,226],"mutant":[84,104,129,142],"lines":[85,105],"diverse":[88],"panel":[89],"inhibitors.":[92],"focus":[94],"compound,":[97],"TCMDC-125334,":[98],"which":[99,112,195],"was":[100],"active":[101],"against":[102],"all":[103],"tested,":[106],"including":[107],"C276Y":[110,128],"line,":[111],"arose":[113],"selections":[115],"with":[116,130,190],"clinical":[118],"candidate":[119],"DSM265.":[120,154],"found":[122],"that":[123],"selection":[124],"TCMDC-125334":[131,148,184],"yielded":[132],"additional":[133],"genetic":[134],"changes":[135],"dhodh":[138],"locus.":[139],"These":[140],"double":[141],"parasites":[143,179,189,219],"exhibited":[144],"decreased":[145],"were":[150,196,202],"highly":[151],"resistant":[152],"Finally,":[155],"tested":[157],"whether":[158],"could":[161],"be":[162],"exploited":[163],"context":[172],"combination":[174],"treatment":[175],"by":[176],"exposing":[177],"wildtype":[178,207],"both":[181,199],"DSM265":[182],"simultaneously.":[185],"This":[186],"selected":[187],"for":[188],"V532A":[193],"mutation":[194],"cross-resistant":[197],"fit":[204,218],"parent":[208],"vitro":[210],".":[211],"The":[212],"these":[215],"cross-resistant,":[216],"evolutionarily":[217],"highlights":[220],"mutational":[222],"flexibility":[223],"enzyme.":[227]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":2}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2023-09-23T00:00:00"}
