{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:32:24Z","timestamp":1790937144338,"version":"4.1.0"},"reference-count":100,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6725","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2024,11,29]]},"abstract":"<jats:p>\n            Surveillance of drug resistance and the discovery of novel targets\u2014key objectives in the fight against malaria\u2014rely on identifying resistance-conferring mutations in\n            <jats:italic>Plasmodium<\/jats:italic>\n            parasites. Current approaches, while successful, require laborious experimentation or large sample sizes. To elucidate shared determinants of antimalarial resistance that can empower in silico inference, we examined the genomes of 724\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            clones, each selected in vitro for resistance to one of 118 compounds. We identified 1448 variants in 128 recurrently mutated genes, including drivers of antimalarial multidrug resistance. In contrast to naturally occurring variants, those selected in vitro are more likely to be missense or frameshift, involve bulky substitutions, and occur in conserved, ordered protein domains. Collectively, our dataset reveals mutation features that predict drug resistance in eukaryotic pathogens.\n          <\/jats:p>","DOI":"10.1126\/science.adk9893","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T19:00:56Z","timestamp":1732820456000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":32,"title":["Systematic in vitro evolution in\n            <i>Plasmodium falciparum<\/i>\n            reveals key determinants of drug resistance"],"prefix":"10.1126","volume":"386","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9059-1200","authenticated-orcid":true,"given":"Madeline R.","family":"Luth","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-0204","authenticated-orcid":true,"given":"Karla P.","family":"Godinez-Macias","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-7029","authenticated-orcid":true,"given":"Daisy","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8680-2351","authenticated-orcid":true,"given":"John","family":"Okombo","sequence":"additional","affiliation":[{"name":"Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Irving Medical Center, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-8638","authenticated-orcid":true,"given":"Vandana","family":"Thathy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA."},{"name":"Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Irving Medical Center, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Global Health Drug Discovery Institute, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9947-7254","authenticated-orcid":true,"given":"Sindhu","family":"Daggupati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-0080","authenticated-orcid":true,"given":"Heledd","family":"Davies","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish K.","family":"Dhingra","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA."},{"name":"Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Irving Medical Center, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5148-0038","authenticated-orcid":true,"given":"Jan M.","family":"Economy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-8625","authenticated-orcid":true,"given":"Rebecca C. 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