{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:04:00Z","timestamp":1790287440805,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pbio.3003192","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000}}],"reference-count":112,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2024-00399013"],"award-info":[{"award-number":["RS-2024-00399013"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2024-00334487"],"award-info":[{"award-number":["RS-2024-00334487"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00265524"],"award-info":[{"award-number":["RS-2023-00265524"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00212238"],"award-info":[{"award-number":["RS-2023-00212238"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2024-00446438"],"award-info":[{"award-number":["RS-2024-00446438"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010446","name":"Institute for Basic Science","doi-asserted-by":"publisher","award":["IBS-R002-D1"],"award-info":[{"award-number":["IBS-R002-D1"]}],"id":[{"id":"10.13039\/501100010446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018749","name":"Korea Brain Research Institute","doi-asserted-by":"publisher","award":["25-BR-01-03"],"award-info":[{"award-number":["25-BR-01-03"]}],"id":[{"id":"10.13039\/100018749","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003708","name":"Korea Institute of Science and Technology Information","doi-asserted-by":"crossref","award":["K-24-L2-M1-C4"],"award-info":[{"award-number":["K-24-L2-M1-C4"]}],"id":[{"id":"10.13039\/501100003708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003708","name":"Korea Institute of Science and Technology Information","doi-asserted-by":"crossref","award":["K-24-L2-M1-C4"],"award-info":[{"award-number":["K-24-L2-M1-C4"]}],"id":[{"id":"10.13039\/501100003708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["C523100"],"award-info":[{"award-number":["C523100"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["C523100"],"award-info":[{"award-number":["C523100"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>Neurodevelopmental disorders can have long-lasting effects, causing not only early pediatric symptoms but also a range of neurological issues throughout adulthood. West syndrome is a severe neurodevelopmental disorder marked by infantile spasms, an early symptom that typically subsides with age. However, many patients progress to other seizure forms, known as seizure evolution, which is closely linked to poor long-term outcomes. Despite its clinical significance, the neurobiological mechanisms behind seizure evolution in West syndrome remain poorly understood. Recent genetic studies have consistently identified the <jats:italic>CYFIP2<\/jats:italic> p.Arg87Cys variant in West syndrome patients, and the <jats:italic><jats:italic>Cyfip2<\/jats:italic><\/jats:italic><jats:sup>+<jats:italic>\/R87C<\/jats:italic><\/jats:sup> mouse model carrying this mutation has been shown to recapitulate key symptoms of the disorder, including infantile spasms. In this study, we aimed to gain deeper insight into seizure evolution by conducting longitudinal deep phenotyping of the <jats:italic><jats:italic>Cyfip2<\/jats:italic><\/jats:italic><jats:sup>+<jats:italic>\/R87C<\/jats:italic><\/jats:sup> mouse model from the neonatal stage to seven months of age. We tracked seizure activity through behavioral and EEG recordings and employed multi-omic analyses, including tissue and single-cell level transcriptomics, ultrastructural analysis, proteomics, and lipidomics, to capture a comprehensive view of molecular and cellular changes. Our results showed that after an initial period of neonatal spasms, <jats:italic><jats:italic>Cyfip2<\/jats:italic><\/jats:italic><jats:sup>+<jats:italic>\/R87C<\/jats:italic><\/jats:sup> mice entered a seizure-free phase, followed by spontaneous recurrent seizures in adulthood, ultimately leading to premature death. This progression was associated with synaptic remodeling, sequential activation of different glial cell types, lipid droplet accumulation in astrocytes, and significant proteomic and lipidomic changes in the brain. These findings suggest that seizure evolution in West syndrome involves complex, time-dependent interactions between neurons and glial cells, along with alterations in lipid metabolism. Our study highlights the potential of longitudinal multi-omic approaches to uncover underlying mechanisms of seizure evolution and suggests that targeting these changes could offer novel therapeutic strategies. Additionally, the dataset generated here may provide valuable insights for other epilepsy and neurodevelopmental disorder models.<\/jats:p>","DOI":"10.1371\/journal.pbio.3003192","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:56:33Z","timestamp":1760032593000},"page":"e3003192","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism"],"prefix":"10.1371","volume":"23","author":[{"given":"Ruiying","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muwon","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyu Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyojin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeji","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hea Ji","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungji","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungsoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukyung","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U Suk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyae Rim","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonhee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulim","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woosuk","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serk In","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunha","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geum-Sook","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngae","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kea Joo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-2152","authenticated-orcid":true,"given":"Kihoon","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"issue":"4","key":"pbio.3003192.ref001","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1474-4422(24)00038-3","article-title":"Global, regional, and national burden of disorders affecting the nervous system, 1990\u20132021: a systematic analysis for the Global Burden of Disease Study 2021","volume":"23","author":"GBD 2021 Nervous System Disorders Collaborators","year":"2024","journal-title":"Lancet Neurol"},{"issue":"1","key":"pbio.3003192.ref002","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41572-024-00546-6","article-title":"Developmental and epileptic encephalopathies","volume":"10","author":"IE Scheffer","year":"2024","journal-title":"Nat Rev Dis Primers"},{"issue":"12","key":"pbio.3003192.ref003","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1007\/s10072-020-04600-5","article-title":"West syndrome: a comprehensive review","volume":"41","author":"P Pavone","year":"2020","journal-title":"Neurol Sci"},{"key":"pbio.3003192.ref004","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/epi4.12008","article-title":"Long-term mortality of patients with West syndrome","volume":"1","author":"M Sillanp\u00e4\u00e4","year":"2016","journal-title":"Epilepsia Open"},{"key":"pbio.3003192.ref005","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1528-1167.2011.03177.x","article-title":"Definition and natural history of Lennox\u2013Gastaut syndrome","volume":"52","author":"PR Camfield","year":"2011","journal-title":"Epilepsia"},{"issue":"4","key":"pbio.3003192.ref006","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1111\/epi.16468","article-title":"Mortality in infantile spasms: a hospital-based study","volume":"61","author":"C Harini","year":"2020","journal-title":"Epilepsia"},{"issue":"2","key":"pbio.3003192.ref007","doi-asserted-by":"crossref","first-page":"107","DOI":"10.5698\/1535-7597.18.2.107","article-title":"Utilizing animal models of infantile spasms","volume":"18","author":"CG Dulla","year":"2018","journal-title":"Epilepsy Curr"},{"issue":"2","key":"pbio.3003192.ref008","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/epi.17841","article-title":"Mechanisms of infantile epileptic spasms syndrome: what have we learned from animal models?","volume":"65","author":"AC Ng","year":"2024","journal-title":"Epilepsia"},{"issue":"6","key":"pbio.3003192.ref009","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1080\/19768354.2019.1696406","article-title":"Differential cell-type-expression of CYFIP1 and CYFIP2 in the adult mouse hippocampus","volume":"23","author":"Y Zhang","year":"2019","journal-title":"Anim Cells Syst (Seoul)"},{"issue":"5","key":"pbio.3003192.ref010","doi-asserted-by":"crossref","first-page":"304","DOI":"10.5483\/BMBRep.2019.52.5.097","article-title":"Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy","volume":"52","author":"Y Zhang","year":"2019","journal-title":"BMB Rep"},{"issue":"1","key":"pbio.3003192.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2020.05.221","article-title":"Epilepsy- and intellectual disability-associated CYFIP2 interacts with both actin regulators and RNA-binding proteins in the neonatal mouse forebrain","volume":"529","author":"Y Lee","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"issue":"19","key":"pbio.3003192.ref012","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1093\/hmg\/ddae107","article-title":"Neurodevelopmental disorder-associated CYFIP2 regulates membraneless organelles and eIF2\u03b1 phosphorylation via protein interactors and actin cytoskeleton","volume":"33","author":"Y Zhang","year":"2024","journal-title":"Hum Mol Genet"},{"issue":"7","key":"pbio.3003192.ref013","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1093\/hmg\/ddu595","article-title":"Fragile X-like behaviors and abnormal cortical dendritic spines in cytoplasmic FMR1-interacting protein 2-mutant mice","volume":"24","author":"K Han","year":"2015","journal-title":"Hum Mol Genet"},{"issue":"8","key":"pbio.3003192.ref014","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/j.celrep.2019.01.092","article-title":"Autism and schizophrenia-associated CYFIP1 regulates the balance of synaptic excitation and inhibition","volume":"26","author":"EC Davenport","year":"2019","journal-title":"Cell Rep"},{"issue":"3","key":"pbio.3003192.ref015","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/ana.25827","article-title":"Haploinsufficiency of Cyfip2 causes lithium-responsive prefrontal dysfunction","volume":"88","author":"S-H Lee","year":"2020","journal-title":"Ann Neurol"},{"key":"pbio.3003192.ref016","doi-asserted-by":"crossref","first-page":"574947","DOI":"10.3389\/fnmol.2020.574947","article-title":"Enhanced prefrontal neuronal activity and social dominance behavior in postnatal forebrain excitatory neuron-specific Cyfip2 knock-out mice","volume":"13","author":"Y Zhang","year":"2020","journal-title":"Front Mol Neurosci"},{"issue":"4","key":"pbio.3003192.ref017","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/ana.25208","article-title":"De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy","volume":"83","author":"M Nakashima","year":"2018","journal-title":"Ann Neurol"},{"issue":"5","key":"pbio.3003192.ref018","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41431-018-0331-z","article-title":"Spatially clustering de novo variants in CYFIP2, encoding the cytoplasmic FMRP interacting protein 2, cause intellectual disability and seizures","volume":"27","author":"M Zweier","year":"2019","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"pbio.3003192.ref019","doi-asserted-by":"crossref","first-page":"104302","DOI":"10.1016\/j.braindev.2024.104302","article-title":"Recent advances in CYFIP2-associated neurodevelopmental disorders: from human genetics to molecular mechanisms and mouse models","volume":"47","author":"R Ma","year":"2025","journal-title":"Brain Dev"},{"issue":"12","key":"pbio.3003192.ref020","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1111\/cns.12860","article-title":"Novel West syndrome candidate genes in a Chinese cohort","volume":"24","author":"J Peng","year":"2018","journal-title":"CNS Neurosci Ther"},{"issue":"3","key":"pbio.3003192.ref021","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41436-020-01011-x","article-title":"New insights into the clinical and molecular spectrum of the novel CYFIP2-related neurodevelopmental disorder and impairment of the WRC-mediated actin dynamics","volume":"23","author":"A Begemann","year":"2021","journal-title":"Genet Med"},{"issue":"1","key":"pbio.3003192.ref022","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/ana.26535","article-title":"CYFIP2 p.Arg87Cys causes neurological defects and degradation of CYFIP2","volume":"93","author":"M Kang","year":"2023","journal-title":"Ann Neurol"},{"issue":"2","key":"pbio.3003192.ref023","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0006-8993(90)91601-C","article-title":"Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy","volume":"535","author":"CR Houser","year":"1990","journal-title":"Brain Res"},{"issue":"5","key":"pbio.3003192.ref024","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ana.25598","article-title":"Reduced CYFIP2 stability by Arg87 variants causing human neurological disorders","volume":"86","author":"Y Lee","year":"2019","journal-title":"Ann Neurol"},{"issue":"43","key":"pbio.3003192.ref025","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pbio.3003192.ref026","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.tins.2020.01.003","article-title":"Astrocytes and microglia: in sickness and in health","volume":"43","author":"ID Vainchtein","year":"2020","journal-title":"Trends Neurosci"},{"issue":"1","key":"pbio.3003192.ref027","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuron.2012.12.023","article-title":"Microglia: new roles for the synaptic stripper","volume":"77","author":"H Kettenmann","year":"2013","journal-title":"Neuron"},{"issue":"6","key":"pbio.3003192.ref028","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1194\/jlr.M072454","article-title":"Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH","volume":"58","author":"GN Ioannou","year":"2017","journal-title":"J Lipid Res"},{"issue":"34","key":"pbio.3003192.ref029","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2205475119","article-title":"Examining atherosclerotic lesions in three dimensions at the nanometer scale with cryo-FIB-SEM","volume":"119","author":"J Capua-Shenkar","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7293","key":"pbio.3003192.ref030","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/nature08938","article-title":"NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"P Duewell","year":"2010","journal-title":"Nature"},{"issue":"1","key":"pbio.3003192.ref031","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13578-022-00828-0","article-title":"Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases","volume":"12","author":"D Yang","year":"2022","journal-title":"Cell Biosci"},{"issue":"11","key":"pbio.3003192.ref032","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"S Aibar","year":"2017","journal-title":"Nat Methods"},{"issue":"2","key":"pbio.3003192.ref033","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","article-title":"NicheNet: modeling intercellular communication by linking ligands to target genes","volume":"17","author":"R Browaeys","year":"2020","journal-title":"Nat Methods"},{"issue":"1","key":"pbio.3003192.ref034","article-title":"Neurexin-2: an inhibitory neurexin that restricts excitatory synapse formation in the hippocampus","volume":"9","author":"P-Y Lin","year":"2023","journal-title":"Sci Adv"},{"issue":"3","key":"pbio.3003192.ref035","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41583-020-00415-7","article-title":"Neurexins: molecular codes for shaping neuronal synapses","volume":"22","author":"AM Gomez","year":"2021","journal-title":"Nat Rev Neurosci"},{"issue":"4","key":"pbio.3003192.ref036","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.tibs.2024.01.011","article-title":"Mitochondria in disease: changes in shapes and dynamics","volume":"49","author":"BC Jenkins","year":"2024","journal-title":"Trends Biochem Sci"},{"issue":"11","key":"pbio.3003192.ref037","doi-asserted-by":"crossref","first-page":"108132","DOI":"10.1016\/j.celrep.2020.108132","article-title":"Cell-type- and brain-region-resolved mouse brain lipidome","volume":"32","author":"D Fitzner","year":"2020","journal-title":"Cell Rep"},{"key":"pbio.3003192.ref038","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3389\/fnana.2014.00142","article-title":"Barriers in the brain: resolving dendritic spine morphology and compartmentalization","volume":"8","author":"M Adrian","year":"2014","journal-title":"Front Neuroanat"},{"issue":"3","key":"pbio.3003192.ref039","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.neuron.2013.10.022","article-title":"Neurotransmitter release: the last millisecond in the life of a synaptic vesicle","volume":"80","author":"TC S\u00fcdhof","year":"2013","journal-title":"Neuron"},{"key":"pbio.3003192.ref040","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuroscience.2012.03.048","article-title":"Dendritic spine pathology in epilepsy: cause or consequence?","volume":"251","author":"M Wong","year":"2013","journal-title":"Neuroscience"},{"issue":"2","key":"pbio.3003192.ref041","article-title":"Depolarization and CaM kinase IV modulate NMDA receptor splicing through two essential RNA elements","volume":"5","author":"J-A Lee","year":"2007","journal-title":"PLoS Biol"},{"issue":"5","key":"pbio.3003192.ref042","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrn.2016.27","article-title":"The neurogenetics of alternative splicing","volume":"17","author":"CK Vuong","year":"2016","journal-title":"Nat Rev Neurosci"},{"key":"pbio.3003192.ref043","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.brainres.2015.09.027","article-title":"Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis","volume":"1627","author":"Y Luo","year":"2015","journal-title":"Brain Res"},{"issue":"2","key":"pbio.3003192.ref044","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/neup.12410","article-title":"Marked accumulation of oligodendroglia-like cells in temporal lobe epilepsy with amygdala enlargement and hippocampal sclerosis","volume":"38","author":"D Sone","year":"2018","journal-title":"Neuropathology"},{"key":"pbio.3003192.ref045","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.neuroscience.2024.11.050","article-title":"Adolescent seizure impacts oligodendrocyte maturation, neuronal-glial circuit formation, and myelination in the mammalian forebrain","volume":"564","author":"K Foutch","year":"2025","journal-title":"Neuroscience"},{"issue":"9","key":"pbio.3003192.ref046","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.135391","article-title":"Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus","volume":"6","author":"F Sano","year":"2021","journal-title":"JCI Insight"},{"issue":"5","key":"pbio.3003192.ref047","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41583-019-0126-4","article-title":"Neuron-glia interactions in the pathophysiology of epilepsy","volume":"20","author":"DC Patel","year":"2019","journal-title":"Nat Rev Neurosci"},{"key":"pbio.3003192.ref048","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3389\/fncel.2019.00042","article-title":"Glial control of synapse number in healthy and diseased brain","volume":"13","author":"E Lee","year":"2019","journal-title":"Front Cell Neurosci"},{"issue":"10","key":"pbio.3003192.ref049","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1038\/s41593-022-01170-x","article-title":"Oligodendrocyte precursor cells engulf synapses during circuit remodeling in mice","volume":"25","author":"YSS Auguste","year":"2022","journal-title":"Nat Neurosci"},{"key":"pbio.3003192.ref050","doi-asserted-by":"crossref","first-page":"102925","DOI":"10.1016\/j.conb.2024.102925","article-title":"Astrocyte-neuron crosstalk in neurodevelopmental disorders","volume":"89","author":"G S\u00e9journ\u00e9","year":"2024","journal-title":"Curr Opin Neurobiol"},{"issue":"5","key":"pbio.3003192.ref051","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/s41593-022-01052-2","article-title":"Maladaptive myelination promotes generalized epilepsy progression","volume":"25","author":"JK Knowles","year":"2022","journal-title":"Nat Neurosci"},{"key":"pbio.3003192.ref052","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuropharm.2015.08.046","article-title":"Adenosinergic signaling in epilepsy","volume":"104","author":"D Boison","year":"2016","journal-title":"Neuropharmacology"},{"issue":"8","key":"pbio.3003192.ref053","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nn880","article-title":"Antagonists of GLU(K5)-containing kainate receptors prevent pilocarpine-induced limbic seizures","volume":"5","author":"I Smolders","year":"2002","journal-title":"Nat Neurosci"},{"issue":"5563","key":"pbio.3003192.ref054","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1126\/science.1067859","article-title":"Control of synaptic strength by glial TNFalpha","volume":"295","author":"EC Beattie","year":"2002","journal-title":"Science"},{"issue":"7087","key":"pbio.3003192.ref055","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/nature04671","article-title":"Synaptic scaling mediated by glial TNF-alpha","volume":"440","author":"D Stellwagen","year":"2006","journal-title":"Nature"},{"issue":"6","key":"pbio.3003192.ref056","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.bbi.2008.03.009","article-title":"The role of cytokines in the pathophysiology of epilepsy","volume":"22","author":"A Vezzani","year":"2008","journal-title":"Brain Behav Immun"},{"issue":"1","key":"pbio.3003192.ref057","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41420-023-01504-z","article-title":"The regulatory role of lipophagy in central nervous system diseases","volume":"9","author":"Z-Q Lan","year":"2023","journal-title":"Cell Death Discov"},{"issue":"1","key":"pbio.3003192.ref058","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/s41467-017-01186-z","article-title":"Hyperlipidemia-induced cholesterol crystal production by endothelial cells promotes atherogenesis","volume":"8","author":"Y Baumer","year":"2017","journal-title":"Nat Commun"},{"issue":"8","key":"pbio.3003192.ref059","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s41574-023-00845-0","article-title":"Lipid droplet biogenesis and functions in health and disease","volume":"19","author":"A Zadoorian","year":"2023","journal-title":"Nat Rev Endocrinol"},{"issue":"6","key":"pbio.3003192.ref060","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41582-022-00651-8","article-title":"The metabolic basis of epilepsy","volume":"18","author":"JM Rho","year":"2022","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"pbio.3003192.ref061","first-page":"1289","article-title":"Mitochondrial dysfunction of astrocytes mediates lipid accumulation in temporal lobe epilepsy","volume":"15","author":"Y Su","year":"2024","journal-title":"Aging Dis"},{"issue":"6","key":"pbio.3003192.ref062","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.cell.2019.04.001","article-title":"Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity","volume":"177","author":"MS Ioannou","year":"2019","journal-title":"Cell"},{"issue":"8","key":"pbio.3003192.ref063","doi-asserted-by":"crossref","first-page":"107498","DOI":"10.1016\/j.jbc.2024.107498","article-title":"Bridging lipid metabolism and mitochondrial genome maintenance","volume":"300","author":"C Boone","year":"2024","journal-title":"J Biol Chem"},{"issue":"2","key":"pbio.3003192.ref064","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/brain\/awy320","article-title":"The role of astrocytes in seizure generation: insights from a novel in vitro seizure model based on mitochondrial dysfunction","volume":"142","author":"F Chan","year":"2019","journal-title":"Brain"},{"issue":"4","key":"pbio.3003192.ref065","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41593-023-01288-6","article-title":"Lipid-accumulated reactive astrocytes promote disease progression in epilepsy","volume":"26","author":"Z-P Chen","year":"2023","journal-title":"Nat Neurosci"},{"issue":"8","key":"pbio.3003192.ref066","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/s42255-023-00835-6","article-title":"Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition","volume":"5","author":"B Morant-Ferrando","year":"2023","journal-title":"Nat Metab"},{"issue":"3","key":"pbio.3003192.ref067","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s42255-023-00756-4","article-title":"Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration","volume":"5","author":"Y Mi","year":"2023","journal-title":"Nat Metab"},{"issue":"37","key":"pbio.3003192.ref068","article-title":"Brain lipidomics: from functional landscape to clinical significance","volume":"8","author":"JH Yoon","year":"2022","journal-title":"Sci Adv"},{"issue":"3","key":"pbio.3003192.ref069","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.neuron.2023.10.023","article-title":"Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist","volume":"112","author":"A Litvinchuk","year":"2024","journal-title":"Neuron"},{"issue":"10","key":"pbio.3003192.ref070","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1111\/epi.17367","article-title":"A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox\u2013Gastaut syndrome (ELEKTRA)","volume":"63","author":"CD Hahn","year":"2022","journal-title":"Epilepsia"},{"issue":"27","key":"pbio.3003192.ref071","doi-asserted-by":"crossref","first-page":"8752","DOI":"10.1523\/JNEUROSCI.0915-09.2009","article-title":"A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10\u00a0+\u00a07, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment","volume":"29","author":"MG Price","year":"2009","journal-title":"J Neurosci"},{"issue":"12","key":"pbio.3003192.ref072","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1093\/hmg\/ddy122","article-title":"A new mouse model of ARX dup24 recapitulates the patients\u2019 behavioral and fine motor alterations","volume":"27","author":"A Dubos","year":"2018","journal-title":"Hum Mol Genet"},{"issue":"5","key":"pbio.3003192.ref073","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1093\/brain\/awy046","article-title":"Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy","volume":"141","author":"J Kovacevic","year":"2018","journal-title":"Brain"},{"key":"pbio.3003192.ref074","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.48705","article-title":"Stxbp1\/Munc18-1 haploinsufficiency impairs inhibition and mediates key neurological features of STXBP1 encephalopathy","volume":"9","author":"W Chen","year":"2020","journal-title":"Elife"},{"issue":"11","key":"pbio.3003192.ref075","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.medj.2022.08.006","article-title":"Evaluating human mutation databases for \u201ctreatability\u201d using patient-customized therapy","volume":"3","author":"S Mittal","year":"2022","journal-title":"Med"},{"issue":"2","key":"pbio.3003192.ref076","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/jnc.15622","article-title":"Protein interactome and cell-type expression analyses reveal that cytoplasmic FMR1-interacting protein 1 (CYFIP1), but not CYFIP2, associates with astrocytic focal adhesion","volume":"162","author":"R Ma","year":"2022","journal-title":"J Neurochem"},{"issue":"1","key":"pbio.3003192.ref077","doi-asserted-by":"crossref","first-page":"9802","DOI":"10.1038\/s41467-024-54077-5","article-title":"A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases","volume":"15","author":"O Kim-McManus","year":"2024","journal-title":"Nat Commun"},{"key":"pbio.3003192.ref078","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3389\/fnmol.2018.00482","article-title":"Smaller body size, early postnatal lethality, and cortical extracellular matrix-related gene expression changes of Cyfip2-null embryonic mice","volume":"11","author":"Y Zhang","year":"2019","journal-title":"Front Mol Neurosci"},{"issue":"12","key":"pbio.3003192.ref079","doi-asserted-by":"crossref","first-page":"111398","DOI":"10.1016\/j.celrep.2022.111398","article-title":"Postnatal age-differential ASD-like transcriptomic, synaptic, and behavioral deficits in Myt1l-mutant mice","volume":"40","author":"S Kim","year":"2022","journal-title":"Cell Rep"},{"key":"pbio.3003192.ref080","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3389\/fnmol.2018.00250","article-title":"Integrative brain transcriptome analysis reveals region-specific and broad molecular changes in Shank3-overexpressing mice","volume":"11","author":"C Jin","year":"2018","journal-title":"Front Mol Neurosci"},{"issue":"4","key":"pbio.3003192.ref081","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":"12","key":"pbio.3003192.ref082","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"},{"key":"pbio.3003192.ref083","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences","volume":"4","author":"C Soneson","year":"2015","journal-title":"F1000Res"},{"issue":"5","key":"pbio.3003192.ref084","article-title":"DAVID: database for annotation, visualization, and integrated discovery","volume":"4","author":"Jr Dennis G","year":"2003","journal-title":"Genome Biol"},{"issue":"11","key":"pbio.3003192.ref085","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0013984","article-title":"Enrichment map: a network-based method for gene-set enrichment visualization and interpretation","volume":"5","author":"D Merico","year":"2010","journal-title":"PLoS One"},{"key":"pbio.3003192.ref086","doi-asserted-by":"crossref","first-page":"141","DOI":"10.12688\/f1000research.4536.1","article-title":"Enrichment Map - a Cytoscape app to visualize and explore OMICs pathway enrichment results","volume":"3","author":"R Isserlin","year":"2014","journal-title":"F1000Res"},{"issue":"51","key":"pbio.3003192.ref087","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data","volume":"111","author":"S Shen","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3003192.ref088","doi-asserted-by":"crossref","first-page":"614435","DOI":"10.3389\/fnmol.2020.614435","article-title":"The neomycin resistance cassette in the targeted allele of Shank3B knock-out mice has potential off-target effects to produce an unusual Shank3 isoform","volume":"13","author":"C Jin","year":"2021","journal-title":"Front Mol Neurosci"},{"issue":"9","key":"pbio.3003192.ref089","article-title":"Regulated RalBP1 binding to RalA and PSD-95 controls AMPA receptor endocytosis and LTD","volume":"7","author":"K Han","year":"2009","journal-title":"PLoS Biol"},{"issue":"6","key":"pbio.3003192.ref090","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/jnc.14796","article-title":"Shank3 regulates striatal synaptic abundance of Cyld, a deubiquitinase specific for Lys63-linked polyubiquitin chains","volume":"150","author":"C Jin","year":"2019","journal-title":"J Neurochem"},{"issue":"6","key":"pbio.3003192.ref091","article-title":"Real-time live imaging of osteoclast activation via Cathepsin K activity in bone diseases","volume":"63","author":"S Koo","year":"2024","journal-title":"Angew Chem Int Ed Engl"},{"issue":"1","key":"pbio.3003192.ref092","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41413-023-00255-y","article-title":"Mobilization of monocytic myeloid-derived suppressor cells is regulated by PTH1R activation in bone marrow stromal cells","volume":"11","author":"EJ Lee","year":"2023","journal-title":"Bone Res"},{"key":"pbio.3003192.ref093","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3389\/fnmol.2018.00209","article-title":"Shank2 deletion in parvalbumin neurons leads to moderate hyperactivity, enhanced self-grooming and suppressed seizure susceptibility in mice","volume":"11","author":"S Lee","year":"2018","journal-title":"Front Mol Neurosci"},{"issue":"5","key":"pbio.3003192.ref094","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/nan.12686","article-title":"RAPGEF2 mediates oligomeric A\u03b2-induced synaptic loss and cognitive dysfunction in the 3xTg-AD mouse model of Alzheimer\u2019s disease","volume":"47","author":"Y-N Jang","year":"2021","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"2","key":"pbio.3003192.ref095","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Y Hao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"pbio.3003192.ref096","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13059-015-0844-5","article-title":"MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data","volume":"16","author":"G Finak","year":"2015","journal-title":"Genome Biol"},{"key":"pbio.3003192.ref097","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baz046","article-title":"PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data","volume":"2019","author":"O Franz\u00e9n","year":"2019","journal-title":"Database (Oxford)"},{"issue":"1","key":"pbio.3003192.ref098","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/pro.3307","article-title":"The human protein atlas: a spatial map of the human proteome","volume":"27","author":"PJ Thul","year":"2018","journal-title":"Protein Sci"},{"key":"pbio.3003192.ref099","first-page":"060012","article-title":"Fast gene set enrichment analysis","volume":"2021","author":"G Korotkevich","year":"2021","journal-title":"bioRxiv"},{"key":"pbio.3003192.ref100","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"MV Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003192.ref101","unstructured":"Morgan M, Dann E. miloR: differential neighbourhood abundance testing on a graph. R Package Version 1.0.0. 2021."},{"issue":"22","key":"pbio.3003192.ref102","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2100293118","article-title":"Detection of differentially abundant cell subpopulations in scRNA-seq data","volume":"118","author":"J Zhao","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pbio.3003192.ref103","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1038\/s41467-020-18873-z","article-title":"Predicting cell-to-cell communication networks using NATMI","volume":"11","author":"R Hou","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"pbio.3003192.ref104","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1038\/s41598-022-07959-x","article-title":"Computation and visualization of cell\u2013cell signaling topologies in single-cell systems data using Connectome","volume":"12","author":"MSB Raredon","year":"2022","journal-title":"Sci Rep"},{"key":"pbio.3003192.ref105","first-page":"507871","article-title":"iTALK: an R package to characterize and illustrate intercellular communication","author":"Y Wang","year":"2019","journal-title":"BioRxiv"},{"issue":"10","key":"pbio.3003192.ref106","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaa183","article-title":"SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics","volume":"48","author":"S Cabello-Aguilar","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"pbio.3003192.ref107","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/bioinformatics\/btr709","article-title":"Robust rank aggregation for gene list integration and meta-analysis","volume":"28","author":"R Kolde","year":"2012","journal-title":"Bioinformatics"},{"issue":"1","key":"pbio.3003192.ref108","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1038\/s41467-022-30755-0","article-title":"Comparison of methods and resources for cell\u2013cell communication inference from single-cell RNA-Seq data","volume":"13","author":"D Dimitrov","year":"2022","journal-title":"Nat Commun"},{"key":"pbio.3003192.ref109","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jprot.2015.07.001","article-title":"ProLuCID: an improved SEQUEST-like algorithm with enhanced sensitivity and specificity","volume":"129","author":"T Xu","year":"2015","journal-title":"J Proteomics"},{"issue":"15","key":"pbio.3003192.ref110","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1093\/bioinformatics\/btu151","article-title":"Census 2: isobaric labeling data analysis","volume":"30","author":"SKR Park","year":"2014","journal-title":"Bioinformatics"},{"issue":"9","key":"pbio.3003192.ref111","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"S Tyanova","year":"2016","journal-title":"Nat Methods"},{"issue":"1","key":"pbio.3003192.ref112","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Y Zhou","year":"2019","journal-title":"Nat Commun"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3003192","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T17:51:36Z","timestamp":1760464296000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003192"}},"subtitle":[],"editor":[{"given":"Kelly R.","family":"Monk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":112,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003192","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pbio.3003192","asserted-by":"object"}]},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]}}}