Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years
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Published:2023-11-23
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Huschner Franz, Głowacka-Walas JagodaORCID, Mills James D., Klonowska Katarzyna, Lasseter Kathryn, Asara John M., Moavero Romina, Hertzberg Christoph, Weschke BernhardORCID, Riney Kate, Feucht Martha, Scholl Theresa, Krsek Pavel, Nabbout Rima, Jansen Anna C., Petrák Bořivoj, van Scheppingen Jackelien, Zamecnik Josef, Iyer AnandORCID, Anink Jasper J., Mühlebner Angelika, Mijnsbergen Caroline, Lagae Lieven, Curatolo Paolo, Borkowska Julita, Sadowski Krzysztof, Domańska-Pakieła Dorota, Blazejczyk Magdalena, Jansen Floor E., Janson Stef, Urbanska MalgorzataORCID, Tempes Aleksandra, Janssen Bart, Sijko KamilORCID, Wojdan Konrad, Jozwiak SergiuszORCID, Kotulska KatarzynaORCID, Lehmann Karola, Aronica Eleonora, Jaworski Jacek, Kwiatkowski David J.ORCID
Abstract
AbstractWe present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC.
Funder
European Commission
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference53 articles.
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