{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T15:55:47Z","timestamp":1772726147032,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011648","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173179"],"award-info":[{"award-number":["82173179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471214"],"award-info":[{"award-number":["32471214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2023ZYD0128"],"award-info":[{"award-number":["2023ZYD0128"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2024NSFSC0059"],"award-info":[{"award-number":["2024NSFSC0059"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Aging is associated with alternative splicing (AS) defects that have broad implications on aging-associated disorders. However, which drug(s) can rescue age-related AS defects and extend lifespan has not been systematically explored. We performed large-scale compound screening in <jats:italic>C. elegans<\/jats:italic> using a dual-fluorescent splicing reporter system. Among the top hits, doxifluridine, a fluoropyrimidine derivative, rescues age-associated AS defects and extends lifespan. Combining bacterial DNA sequencing, proteomics, metabolomics and the three-way screen system, we further revealed that bacterial ribonucleotide metabolism plays an essential role in doxifluridine conversion and efficacy. Furthermore, doxifluridine increases production of bacterial metabolites, such as linoleic acid and agmatine, to prolong host lifespan. Together, our results identify doxifluridine as a potent lead compound for rescuing aging-associated AS defects and extending lifespan, and elucidate\u00a0drug\u2019s\u00a0functions through complex interplay among drug, bacteria and host.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011648","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T20:34:05Z","timestamp":1743453245000},"page":"e1011648","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Doxifluridine promotes host longevity through bacterial metabolism"],"prefix":"10.1371","volume":"21","author":[{"given":"Rui","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuling","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3621-8151","authenticated-orcid":true,"given":"Xinyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8175-2508","authenticated-orcid":true,"given":"Ran","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongyao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaojia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lunzhi","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-6134","authenticated-orcid":true,"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6041-4454","authenticated-orcid":true,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"issue":"2","key":"pgen.1011648.ref001","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: an expanding universe","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","journal-title":"Cell"},{"issue":"7","key":"pgen.1011648.ref002","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","article-title":"The proteostasis network and its decline in ageing","volume":"20","author":"MS Hipp","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"7288","key":"pgen.1011648.ref003","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature08980","article-title":"The genetics of ageing","volume":"464","author":"CJ Kenyon","year":"2010","journal-title":"Nature"},{"issue":"12","key":"pgen.1011648.ref004","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1007\/s11427-022-2161-3","article-title":"The landscape of aging","volume":"65","author":"Y Cai","year":"2022","journal-title":"Sci China Life Sci"},{"issue":"3","key":"pgen.1011648.ref005","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nrg3662","article-title":"Coupling mRNA processing with transcription in time and space","volume":"15","author":"DL Bentley","year":"2014","journal-title":"Nat Rev Genet"},{"issue":"7280","key":"pgen.1011648.ref006","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature08909","article-title":"Expansion of the eukaryotic proteome by alternative splicing","volume":"463","author":"TW Nilsen","year":"2010","journal-title":"Nature"},{"issue":"4","key":"pgen.1011648.ref007","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41580-022-00545-z","article-title":"The physiology of alternative splicing","volume":"24","author":"LE Marasco","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pgen.1011648.ref008","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2006.06.023","article-title":"Alternative splicing: new insights from global analyses","volume":"126","author":"BJ Blencowe","year":"2006","journal-title":"Cell"},{"issue":"7635","key":"pgen.1011648.ref009","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature20789","article-title":"Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans","volume":"541","author":"C Heintz","year":"2017","journal-title":"Nature"},{"issue":"3","key":"pgen.1011648.ref010","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00439-019-02094-6","article-title":"Alternative splicing in aging and longevity","volume":"139","author":"M Bhadra","year":"2020","journal-title":"Hum Genet"},{"key":"pgen.1011648.ref011","first-page":"10.1038\/d41586-023-01662","article-title":"RNA splicing targets age-related diseases","author":"C Evans-Pughe","year":"2023","journal-title":"Nature"},{"issue":"7","key":"pgen.1011648.ref012","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1093\/nar\/gkt097","article-title":"Position-dependent and neuron-specific splicing regulation by the CELF family RNA-binding protein UNC-75 in Caenorhabditis elegans","volume":"41","author":"H Kuroyanagi","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pgen.1011648.ref013","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41580-021-00411-4","article-title":"Molecular mechanisms of dietary restriction promoting health and longevity","volume":"23","author":"CL Green","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"6","key":"pgen.1011648.ref014","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.cell.2018.02.044","article-title":"The human gut microbiome: from association to modulation","volume":"172","author":"TSB Schmidt","year":"2018","journal-title":"Cell"},{"issue":"7","key":"pgen.1011648.ref015","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.cell.2017.11.024","article-title":"Our gut microbiome: the evolving inner self","volume":"171","author":"P Kundu","year":"2017","journal-title":"Cell"},{"key":"pgen.1011648.ref016","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-micro-102215-095513","article-title":"Gut microbiota, inflammation, and colorectal cancer","volume":"70","author":"CA Brennan","year":"2016","journal-title":"Annu Rev Microbiol"},{"issue":"7698","key":"pgen.1011648.ref017","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nature25979","article-title":"Extensive impact of non-antibiotic drugs on human gut bacteria","volume":"555","author":"L Maier","year":"2018","journal-title":"Nature"},{"issue":"7762","key":"pgen.1011648.ref018","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","article-title":"Mapping human microbiome drug metabolism by gut bacteria and their genes","volume":"570","author":"M Zimmermann","year":"2019","journal-title":"Nature"},{"issue":"7877","key":"pgen.1011648.ref019","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41586-021-03891-8","article-title":"Bioaccumulation of therapeutic drugs by human gut bacteria","volume":"597","author":"M Kl\u00fcnemann","year":"2021","journal-title":"Nature"},{"issue":"10","key":"pgen.1011648.ref020","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/s41564-022-01226-5","article-title":"Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism","volume":"7","author":"P Spanogiannopoulos","year":"2022","journal-title":"Nat Microbiol"},{"issue":"5","key":"pgen.1011648.ref021","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41684-021-00724-z","article-title":"C. elegans: a biosensor for host-microbe interactions","volume":"50","author":"C Backes","year":"2021","journal-title":"Lab Anim (NY)"},{"issue":"4","key":"pgen.1011648.ref022","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2014.01.047","article-title":"Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits","volume":"156","author":"E Watson","year":"2014","journal-title":"Cell"},{"issue":"11","key":"pgen.1011648.ref023","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.tig.2014.07.010","article-title":"Worms, bacteria, and micronutrients: an elegant model of our diet","volume":"30","author":"LS Yilmaz","year":"2014","journal-title":"Trends Genet"},{"issue":"6","key":"pgen.1011648.ref024","doi-asserted-by":"crossref","first-page":"1299-1312.e29","DOI":"10.1016\/j.cell.2019.08.003","article-title":"Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy","volume":"178","author":"R Pryor","year":"2019","journal-title":"Cell"},{"issue":"1","key":"pgen.1011648.ref025","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1038\/s41467-020-16220-w","article-title":"Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion","volume":"11","author":"W Ke","year":"2020","journal-title":"Nat Commun"},{"issue":"29","key":"pgen.1011648.ref026","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.2174\/092986711797287584","article-title":"Development of 5-Fluorouracil derivatives as anticancer agents","volume":"18","author":"X Pan","year":"2011","journal-title":"Curr Med Chem"},{"issue":"12","key":"pgen.1011648.ref027","doi-asserted-by":"crossref","first-page":"e1005725","DOI":"10.1371\/journal.pgen.1005725","article-title":"Reproductive aging drives protein accumulation in the uterus and limits lifespan in C. elegans","volume":"11","author":"SM Zimmerman","year":"2015","journal-title":"PLoS Genet"},{"issue":"3","key":"pgen.1011648.ref028","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.cell.2017.03.040","article-title":"Host-microbe co-metabolism dictates cancer drug efficacy in C. elegans","volume":"169","author":"TA Scott","year":"2017","journal-title":"Cell"},{"issue":"11","key":"pgen.1011648.ref029","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1242\/dev.125.11.2087","article-title":"sma-1 encodes a betaH-spectrin homolog required for Caenorhabditis elegans morphogenesis","volume":"125","author":"C McKeown","year":"1998","journal-title":"Development"},{"issue":"6","key":"pgen.1011648.ref030","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.cmet.2016.05.024","article-title":"Reversible age-related phenotypes induced during larval quiescence in C. elegans","volume":"23","author":"AE Roux","year":"2016","journal-title":"Cell Metab"},{"issue":"7","key":"pgen.1011648.ref031","doi-asserted-by":"crossref","first-page":"e3002165","DOI":"10.1371\/journal.pbio.3002165","article-title":"Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span","volume":"21","author":"Z Hu","year":"2023","journal-title":"PLoS Biol"},{"issue":"16","key":"pgen.1011648.ref032","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1016\/j.cub.2018.06.035","article-title":"C. elegans eats its own intestine to make yolk leading to multiple senescent pathologies","volume":"28","author":"M Ezcurra","year":"2018","journal-title":"Curr Biol"},{"issue":"3","key":"pgen.1011648.ref033","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.cell.2017.03.046","article-title":"Bacterial metabolism affects the C. elegans response to cancer chemotherapeutics","volume":"169","author":"AP Garcia-Gonzalez","year":"2017","journal-title":"Cell"},{"issue":"3","key":"pgen.1011648.ref034","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1093\/genetics\/161.3.1101","article-title":"Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation","volume":"161","author":"D Garigan","year":"2002","journal-title":"Genetics"},{"issue":"1","key":"pgen.1011648.ref035","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cell.2013.02.035","article-title":"Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism","volume":"153","author":"F Cabreiro","year":"2013","journal-title":"Cell"},{"issue":"2","key":"pgen.1011648.ref036","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.cmet.2013.12.005","article-title":"Adaptive capacity to bacterial diet modulates aging in C. elegans","volume":"19","author":"S Pang","year":"2014","journal-title":"Cell Metab"},{"issue":"4","key":"pgen.1011648.ref037","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0959-8049(96)00491-1","article-title":"Doxifluridine in colorectal cancer patients resistant to 5-fluorouracil (5-FU) containing regimens","volume":"33","author":"E Bajetta","year":"1997","journal-title":"Eur J Cancer"},{"issue":"3","key":"pgen.1011648.ref038","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/bjc.1989.65","article-title":"Enhanced therapeutic efficacy of 5\u2019deoxy-5-fluorouridine in 5-fluorouracil resistant head and neck tumours in relation to 5-fluorouracil metabolising enzymes","volume":"59","author":"GJ Peters","year":"1989","journal-title":"Br J Cancer"},{"issue":"D1","key":"pgen.1011648.ref039","doi-asserted-by":"crossref","first-page":"D212","DOI":"10.1093\/nar\/gky1077","article-title":"RegulonDB v 10.5: tackling challenges to unify classic and high throughput knowledge of gene regulation in E. coli K-12","volume":"47","author":"A Santos-Zavaleta","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"pgen.1011648.ref040","doi-asserted-by":"crossref","first-page":"6607","DOI":"10.1128\/JB.183.22.6607-6619.2001","article-title":"Roles of glutamate synthase, gltBD, and gltF in nitrogen metabolism of Escherichia coli and Klebsiella aerogenes","volume":"183","author":"TJ Goss","year":"2001","journal-title":"J Bacteriol"},{"issue":"2","key":"pgen.1011648.ref041","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.fm.2012.09.024","article-title":"Novel touchdown-PCR method for the detection of putrescine producing gram-negative bacteria in food products","volume":"34","author":"L Wunderlichov\u00e1","year":"2013","journal-title":"Food Microbiol"},{"issue":"1","key":"pgen.1011648.ref042","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12934-022-01742-3","article-title":"High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase","volume":"21","author":"F Yang","year":"2022","journal-title":"Microb Cell Fact"},{"issue":"6","key":"pgen.1011648.ref043","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/bjc.2013.86","article-title":"Adjuvant chemotherapy for gastric cancer: a randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201)","volume":"108","author":"Y-K Kang","year":"2013","journal-title":"Br J Cancer"},{"issue":"3","key":"pgen.1011648.ref044","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1093\/jjco\/hyn003","article-title":"Multi-center phase II study for combination therapy with paclitaxel\/doxifluridine to treat advanced\/recurrent gastric cancer showing resistance to S-1 (OGSG 0302)","volume":"38","author":"H Takiuchi","year":"2008","journal-title":"Jpn J Clin Oncol"},{"issue":"3","key":"pgen.1011648.ref045","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/jjco\/hyf022","article-title":"A phase II study of doxifluridine in elderly patients with advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG 9410)","volume":"32","author":"N Ikeda","year":"2002","journal-title":"Jpn J Clin Oncol"},{"issue":"8","key":"pgen.1011648.ref046","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/oxfordjournals.annonc.a058983","article-title":"Oral doxifluridine in elderly patients with metastatic colorectal cancer: a multicenter phase II study","volume":"5","author":"A Falcone","year":"1994","journal-title":"Ann Oncol"},{"issue":"15","key":"pgen.1011648.ref047","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"AM Bolger","year":"2014","journal-title":"Bioinformatics"},{"issue":"1","key":"pgen.1011648.ref048","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"12","key":"pgen.1011648.ref049","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"4","key":"pgen.1011648.ref050","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"R Patro","year":"2017","journal-title":"Nat Methods"},{"issue":"11","key":"pgen.1011648.ref051","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1038\/s41596-024-01020-z","article-title":"Using clusterProfiler to characterize multiomics data","volume":"19","author":"S Xu","year":"2024","journal-title":"Nat Protoc"},{"key":"pgen.1011648.ref052","volume-title":"Picard toolkit","year":"2019"},{"issue":"17","key":"pgen.1011648.ref053","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1093\/bioinformatics\/btab141","article-title":"ASpli: integrative analysis of splicing landscapes through RNA-Seq assays","volume":"37","author":"E Mancini","year":"2021","journal-title":"Bioinformatics"},{"issue":"9","key":"pgen.1011648.ref054","doi-asserted-by":"crossref","first-page":"e1011477","DOI":"10.1371\/journal.pcbi.1011477","article-title":"Trackplot: a flexible toolkit for combinatorial analysis of genomic data","volume":"19","author":"Y Zhang","year":"2023","journal-title":"PLoS Comput Biol"},{"issue":"7","key":"pgen.1011648.ref055","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.celrep.2015.04.024","article-title":"RNAi interrogation of dietary modulation of development, metabolism, behavior, and aging in C. elegans","volume":"11","author":"R Xiao","year":"2015","journal-title":"Cell Rep"},{"issue":"1","key":"pgen.1011648.ref056","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1002\/cptx.94","article-title":"Generating bacterial foods in toxicology studies with Caenorhabditis elegans","volume":"84","author":"T Ke","year":"2020","journal-title":"Curr Protoc Toxicol"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1011648","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T18:40:59Z","timestamp":1744137659000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011648"}},"subtitle":[],"editor":[{"given":"Daniel A.","family":"Starr","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":56,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011648","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pgen.1011648","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]}}}