{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:43:08Z","timestamp":1789807388222,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009978","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030-184792"],"award-info":[{"award-number":["310030-184792"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013362","name":"Krebsforschung Schweiz","doi-asserted-by":"publisher","award":["4377-02-2018"],"award-info":[{"award-number":["4377-02-2018"]}],"id":[{"id":"10.13039\/501100013362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    The sumoylation (SUMO) pathway is involved in a variety of processes during\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    development, such as gonadal and vulval fate specification, cell cycle progression and maintenance of chromosome structure. The ubiquitous expression and pleiotropic effects have made it difficult to dissect the tissue-specific functions of the SUMO pathway and identify its target proteins. To overcome these challenges, we have established tools to block protein sumoylation and degrade sumoylated target proteins in a tissue-specific and temporally controlled manner. We employed the auxin-inducible protein degradation system (AID) to down-regulate the SUMO E3 ligase GEI-17 or the SUMO ortholog SMO-1, either in the vulval precursor cells (VPCs) or in the gonadal anchor cell (AC). Our results indicate that the SUMO pathway acts in multiple tissues to control different aspects of vulval development, such as AC positioning, basement membrane (BM) breaching, VPC fate specification and morphogenesis. Inhibition of protein sumoylation in the VPCs resulted in abnormal toroid formation and ectopic cell fusions during vulval morphogenesis. In particular, sumoylation of the ETS transcription factor LIN-1 at K169 is necessary for the proper contraction of the ventral vulA toroids. Thus, the SUMO pathway plays several distinct roles throughout vulval development.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009978","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T13:34:56Z","timestamp":1654522496000},"page":"e1009978","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tissue-specific inhibition of protein sumoylation uncovers diverse SUMO functions during C. elegans vulval development"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8574-0141","authenticated-orcid":true,"given":"Aleksandra","family":"Fergin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-4952","authenticated-orcid":true,"given":"Gabriel","family":"Boesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5819-8801","authenticated-orcid":true,"given":"Nadja R.","family":"Greter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-4029","authenticated-orcid":true,"given":"Simon","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-3721","authenticated-orcid":true,"given":"Alex","family":"Hajnal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"pgen.1009978.ref001","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1083\/jcb.140.3.499","article-title":"SUMO-1 Modification and Its Role in Targeting the Ran GTPase-activating Protein, RanGAP1, to the Nuclear Pore Complex","volume":"140","author":"MJ Matunis","year":"1998","journal-title":"J Cell Biol"},{"key":"pgen.1009978.ref002","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0092-8674(00)81862-0","article-title":"A Small Ubiquitin-Related Polypeptide Involved in Targeting RanGAP1 to Nuclear Pore Complex Protein RanBP2","volume":"88","author":"R Mahajan","year":"1997","journal-title":"Cell"},{"key":"pgen.1009978.ref003","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.biochem.73.011303.074118","article-title":"Protein Modification by SUMO","volume":"73","author":"ES Johnson","year":"2004","journal-title":"Annu Rev Biochem"},{"key":"pgen.1009978.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molcel.2005.03.012","article-title":"SUMO.","volume":"18","author":"RT Hay","year":"2005","journal-title":"Mol Cell"},{"key":"pgen.1009978.ref005","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/BJ20100158","article-title":"Mechanisms, regulation and consequences of protein SUMOylation","volume":"428","author":"KA Wilkinson","year":"2010","journal-title":"Biochem J"},{"key":"pgen.1009978.ref006","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev-biochem-061909-093311","article-title":"Sumoylation: A Regulatory Protein Modification in Health and Disease","volume":"82","author":"A Flotho","year":"2013","journal-title":"Annu Rev Biochem"},{"key":"pgen.1009978.ref007","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1534\/genetics.104.036137","article-title":"Systematic, RNA-Interference-Mediated Identification of mus-101 Modifier Genes in Caenorhabditis elegans","volume":"169","author":"AH Holway","year":"2005","journal-title":"Genetics"},{"key":"pgen.1009978.ref008","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1083\/jcb.201307181","article-title":"The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery","volume":"203","author":"HC Ferreira","year":"2013","journal-title":"J Cell Biol"},{"key":"pgen.1009978.ref009","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1038\/ncomms6485","article-title":"Dynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans","volume":"5","author":"F Pelisch","year":"2014","journal-title":"Nat Commun"},{"key":"pgen.1009978.ref010","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nrm3011","article-title":"The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition","volume":"11","author":"JR Gareau","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pgen.1009978.ref011","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1101\/gad.1227104","article-title":"The small ubiquitin-like modifier (SUMO) is required for gonadal and uterine-vulval morphogenesis in Caenorhabditis elegans.","volume":"18","author":"L. Broday","year":"2004","journal-title":"Genes Dev"},{"key":"pgen.1009978.ref012","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/wdev.87","article-title":"Morphogenesis of the Caenorhabditis elegans vulva: Morphogenesis of the C. elegans vulva","volume":"2","author":"AJ Schindler","year":"2013","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"key":"pgen.1009978.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gde.2015.01.006","article-title":"Signal transduction during C. elegans vulval development: a NeverEnding story","volume":"32","author":"T Schmid","year":"2015","journal-title":"Curr Opin Genet Dev"},{"key":"pgen.1009978.ref014","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0092-8674(83)90377-X","article-title":"The lin-12 locus specifies cell fates in Caenorhabditis elegans","volume":"34","author":"I Greenwald","year":"1983","journal-title":"Cell"},{"key":"pgen.1009978.ref015","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0092-8674(85)90230-2","article-title":"lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor","volume":"43","author":"I. Greenwald","year":"1985","journal-title":"Cell"},{"key":"pgen.1009978.ref016","doi-asserted-by":"crossref","first-page":"R311","DOI":"10.1016\/j.cub.2004.03.052","article-title":"Vulval development: the battle between Ras and Notch","volume":"14","author":"MV Sundaram","year":"2004","journal-title":"Curr Biol CB"},{"key":"pgen.1009978.ref017","first-page":"1","article-title":"LIN-12\/Notch signaling in C. elegans.","author":"I. Greenwald","year":"2005","journal-title":"WormBook Online Rev C Elegans Biol"},{"key":"pgen.1009978.ref018","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S1534-5807(03)00168-0","article-title":"Anchor Cell Invasion into the Vulval Epithelium in C. elegans","volume":"5","author":"DR Sherwood","year":"2003","journal-title":"Dev Cell"},{"key":"pgen.1009978.ref019","first-page":"4374","article-title":"The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans","volume":"142","author":"L Zhang","year":"2015","journal-title":"Development"},{"key":"pgen.1009978.ref020","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1242\/dev.01664","article-title":"Sumoylation of LIN-1 promotes transcriptional repression and inhibition of vulval cell fates","volume":"132","author":"ER Leight","year":"2005","journal-title":"Development"},{"key":"pgen.1009978.ref021","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1534\/genetics.114.172668","article-title":"Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated transcriptional repressor to a phosphorylated transcriptional activator","volume":"199","author":"ER Leight","year":"2015","journal-title":"Genetics"},{"key":"pgen.1009978.ref022","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1534\/genetics.104.029017","article-title":"Identification of residues of the Caenorhabditis elegans LIN-1 ETS domain that are necessary for DNA binding and regulation of vulval cell fates","volume":"167","author":"GR Miley","year":"2004","journal-title":"Genetics"},{"key":"pgen.1009978.ref023","first-page":"494","article-title":"Coordinated Lumen Contraction and Expansion during Vulval Tube Morphogenesis in Caenorhabditis elegans.","volume":"23","author":"S Farooqui","year":"2012"},{"key":"pgen.1009978.ref024","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1101\/gad.261917.115","article-title":"Dimerization-driven degradation of C. elegans and human E proteins","volume":"29","author":"MD Sallee","year":"2015","journal-title":"Genes Dev"},{"key":"pgen.1009978.ref025","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1242\/dev.125.6.1083","article-title":"EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans","volume":"125","author":"RD Burdine","year":"1998","journal-title":"Development"},{"key":"pgen.1009978.ref026","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1242\/dev.125.18.3667","article-title":"The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development","volume":"125","author":"DM Eisenmann","year":"1998","journal-title":"Development"},{"key":"pgen.1009978.ref027","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.molcel.2016.11.001","article-title":"A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis","volume":"65","author":"F Pelisch","year":"2017","journal-title":"Mol Cell"},{"key":"pgen.1009978.ref028","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1006\/dbio.1993.1146","article-title":"Isolation and Characterization of Mutations Causing Abnormal Eversion of the Vulva in Caenorhabditis elegans","volume":"157","author":"G Seydoux","year":"1993","journal-title":"Dev Biol"},{"key":"pgen.1009978.ref029","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1038\/sj.emboj.7600726","article-title":"Chromatin regulation and sumoylation in the inhibition of Ras-induced vulval development in Caenorhabditis elegans","volume":"24","author":"G Poulin","year":"2005","journal-title":"EMBO J"},{"key":"pgen.1009978.ref030","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/ncb2233","article-title":"Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine\u2013vulval attachment in Caenorhabditis elegans","volume":"13","author":"S Ihara","year":"2011","journal-title":"Nat Cell Biol"},{"key":"pgen.1009978.ref031","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/ncb1101-983","article-title":"Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia","volume":"3","author":"M K\u00f6ppen","year":"2001","journal-title":"Nat Cell Biol"},{"key":"pgen.1009978.ref032","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1016\/j.cub.2016.06.010","article-title":"MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation","volume":"26","author":"DJ Marston","year":"2016","journal-title":"Curr Biol CB"},{"key":"pgen.1009978.ref033","first-page":"197","article-title":"SUMO Regulation of Cellular Processes.","volume-title":"Sumoylation in Development and Differentiation","author":"AF Deyrieux","year":"2017"},{"key":"pgen.1009978.ref034","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-6358-4_1","article-title":"Concepts and Methodologies to Study Protein SUMOylation: An Overview.","volume":"1475","author":"MJ Matunis","year":"2016","journal-title":"Methods Mol Biol Clifton NJ"},{"key":"pgen.1009978.ref035","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nrm.2016.81","article-title":"A comprehensive compilation of SUMO proteomics","volume":"17","author":"IA Hendriks","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pgen.1009978.ref036","doi-asserted-by":"crossref","first-page":"e1003992","DOI":"10.1371\/journal.pgen.1003992","article-title":"Sumoylated NHR-25\/NR5A regulates cell fate during C. elegans vulval development","volume":"9","author":"JD Ward","year":"2013","journal-title":"PLoS Genet"},{"key":"pgen.1009978.ref037","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ncb1825","article-title":"UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans","volume":"11","author":"JW Ziel","year":"2008","journal-title":"Nat Cell Biol"},{"key":"pgen.1009978.ref038","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1242\/dev.00189","article-title":"A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans","volume":"130","author":"N. Moghal","year":"2003","journal-title":"Development"},{"key":"pgen.1009978.ref039","doi-asserted-by":"crossref","first-page":"14516","DOI":"10.1074\/jbc.M110.157149","article-title":"Small Ubiquitin-related Modifier Ligase Activity of Mms21 Is Required for Maintenance of Chromosome Integrity during the Unperturbed Mitotic Cell Division Cycle in Saccharomyces cerevisiae","volume":"286","author":"R Rai","year":"2011","journal-title":"J Biol Chem"},{"key":"pgen.1009978.ref040","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1242\/dev.00791","article-title":"C. elegans ankyrin repeat protein VAB-19 is a component of epidermal attachment structures and is essential for epidermal morphogenesis","volume":"130","author":"M. Ding","year":"2003","journal-title":"Development"},{"key":"pgen.1009978.ref041","doi-asserted-by":"crossref","first-page":"e17218","DOI":"10.7554\/eLife.17218","article-title":"Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling.","volume":"5","author":"ST McClatchey","year":"2016","journal-title":"eLife"},{"key":"pgen.1009978.ref042","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.devcel.2017.10.024","article-title":"Cell invasion in vivo via rapid exocytosis of a transient lysosome-derived membrane domain","volume":"43","author":"KM Naegeli","year":"2017","journal-title":"Dev Cell"},{"key":"pgen.1009978.ref043","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ydbio.2005.08.007","article-title":"lin-1 has both positive and negative functions in specifying multiple cell fates induced by Ras\/MAP kinase signaling in C. elegans","volume":"286","author":"T Tiensuu","year":"2005","journal-title":"Dev Biol"},{"key":"pgen.1009978.ref044","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/sj.onc.1209789","article-title":"Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation","volume":"26","author":"Z Ji","year":"2007","journal-title":"Oncogene"},{"key":"pgen.1009978.ref045","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/sj.onc.1208226","article-title":"Sumoylation of the net inhibitory domain (NID) is stimulated by PIAS1 and has a negative effect on the transcriptional activity of Net.","volume":"24","author":"C Wasylyk","year":"2005","journal-title":"Oncogene"},{"key":"pgen.1009978.ref046","doi-asserted-by":"crossref","first-page":"38035","DOI":"10.1074\/jbc.M502938200","article-title":"FLI-1 functionally interacts with PIASxalpha, a member of the PIAS E3 SUMO ligase family","volume":"280","author":"E van den Akker","year":"2005","journal-title":"J Biol Chem"},{"key":"pgen.1009978.ref047","first-page":"1","article-title":"ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors","volume":"1826","author":"S Oh","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"pgen.1009978.ref048","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"S. Brenner","year":"1974","journal-title":"Genetics"},{"key":"pgen.1009978.ref049","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1242\/dev.115048","article-title":"Repurposing an endogenous degradation system for rapid and targeted depletion of C. elegans proteins","volume":"141","author":"ST Armenti","year":"2014","journal-title":"Development"},{"key":"pgen.1009978.ref050","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0012-1606(03)00032-0","article-title":"cis-Regulatory control of three cell fate-specific genes in vulval organogenesis of Caenorhabditis elegans and C. briggsae","volume":"257","author":"M Kirouac","year":"2003","journal-title":"Dev Biol"},{"key":"pgen.1009978.ref051","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/msb.2012.51","article-title":"Cell-cycle regulation of NOTCH signaling during C. elegans vulval development","volume":"8","author":"S Nusser-Stein","year":"2012","journal-title":"Mol Syst Biol"},{"key":"pgen.1009978.ref052","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nmeth.1318","article-title":"Enzymatic assembly of DNA molecules up to several hundred kilobases","volume":"6","author":"DG Gibson","year":"2009","journal-title":"Nat Methods"},{"key":"pgen.1009978.ref053","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/ng.248","article-title":"Single-copy insertion of transgenes in Caenorhabditis elegans","volume":"40","author":"C Fr\u00f8kj\u00e6r-Jensen","year":"2008","journal-title":"Nat Genet"},{"key":"pgen.1009978.ref054","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1534\/genetics.115.182162","article-title":"CRISPR-Based Methods for Caenorhabditis elegans Genome Engineering","volume":"202","author":"DJ Dickinson","year":"2016","journal-title":"Genetics"},{"key":"pgen.1009978.ref055","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1534\/genetics.114.169730","article-title":"Efficient marker-free recovery of custom genetic modifications with CRISPR\/Cas9 in Caenorhabditis elegans","volume":"198","author":"JA Arribere","year":"2014","journal-title":"Genetics"},{"key":"pgen.1009978.ref056","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis.","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"pgen.1009978.ref057","doi-asserted-by":"crossref","first-page":"dev199900","DOI":"10.1242\/dev.199900","article-title":"Reciprocal EGFR signaling in the anchor cell ensures precise inter-organ connection during Caenorhabditis elegans vulval morphogenesis","volume":"149","author":"S Spiri","year":"2022","journal-title":"Development"},{"key":"pgen.1009978.ref058","doi-asserted-by":"crossref","first-page":"e1005236","DOI":"10.1371\/journal.pgen.1005236","article-title":"Systemic Regulation of RAS\/MAPK Signaling by the Serotonin Metabolite 5-HIAA.","volume":"11","author":"T Schmid","year":"2015","journal-title":"PLoS Genet."},{"key":"pgen.1009978.ref059","article-title":"Microfluidic-based imaging of complete C. elegans larval development.","author":"S Berger","year":"2021","journal-title":"Development"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1009978","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009978","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T14:02:00Z","timestamp":1655388120000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009978"}},"subtitle":[],"editor":[{"given":"Benjamin","family":"Podbilewicz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,6]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1009978","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.06.471357","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,6]]}}}