Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years
Abstract We 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...
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42855-6 |
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| author | Franz Huschner Jagoda Głowacka-Walas James D. Mills Katarzyna Klonowska Kathryn Lasseter John M. Asara Romina Moavero Christoph Hertzberg Bernhard Weschke Kate Riney Martha Feucht Theresa Scholl Pavel Krsek Rima Nabbout Anna C. Jansen Bořivoj Petrák Jackelien van Scheppingen Josef Zamecnik Anand Iyer Jasper J. Anink Angelika Mühlebner Caroline Mijnsbergen Lieven Lagae Paolo Curatolo Julita Borkowska Krzysztof Sadowski Dorota Domańska-Pakieła Magdalena Blazejczyk Floor E. Jansen Stef Janson Malgorzata Urbanska Aleksandra Tempes Bart Janssen Kamil Sijko Konrad Wojdan Sergiusz Jozwiak Katarzyna Kotulska Karola Lehmann Eleonora Aronica Jacek Jaworski David J. Kwiatkowski |
| author_facet | Franz Huschner Jagoda Głowacka-Walas James D. Mills Katarzyna Klonowska Kathryn Lasseter John M. Asara Romina Moavero Christoph Hertzberg Bernhard Weschke Kate Riney Martha Feucht Theresa Scholl Pavel Krsek Rima Nabbout Anna C. Jansen Bořivoj Petrák Jackelien van Scheppingen Josef Zamecnik Anand Iyer Jasper J. Anink Angelika Mühlebner Caroline Mijnsbergen Lieven Lagae Paolo Curatolo Julita Borkowska Krzysztof Sadowski Dorota Domańska-Pakieła Magdalena Blazejczyk Floor E. Jansen Stef Janson Malgorzata Urbanska Aleksandra Tempes Bart Janssen Kamil Sijko Konrad Wojdan Sergiusz Jozwiak Katarzyna Kotulska Karola Lehmann Eleonora Aronica Jacek Jaworski David J. Kwiatkowski |
| author_sort | Franz Huschner |
| collection | DOAJ |
| description | Abstract We 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. |
| first_indexed | 2024-03-09T15:03:51Z |
| format | Article |
| id | doaj.art-4ebd3a42e79a421f9ec149801b6df580 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T15:03:51Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4ebd3a42e79a421f9ec149801b6df5802023-11-26T13:44:48ZengNature PortfolioNature Communications2041-17232023-11-0114111510.1038/s41467-023-42855-6Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two yearsFranz Huschner0Jagoda Głowacka-Walas1James D. Mills2Katarzyna Klonowska3Kathryn Lasseter4John M. Asara5Romina Moavero6Christoph Hertzberg7Bernhard Weschke8Kate Riney9Martha Feucht10Theresa Scholl11Pavel Krsek12Rima Nabbout13Anna C. Jansen14Bořivoj Petrák15Jackelien van Scheppingen16Josef Zamecnik17Anand Iyer18Jasper J. Anink19Angelika Mühlebner20Caroline Mijnsbergen21Lieven Lagae22Paolo Curatolo23Julita Borkowska24Krzysztof Sadowski25Dorota Domańska-Pakieła26Magdalena Blazejczyk27Floor E. Jansen28Stef Janson29Malgorzata Urbanska30Aleksandra Tempes31Bart Janssen32Kamil Sijko33Konrad Wojdan34Sergiusz Jozwiak35Katarzyna Kotulska36Karola Lehmann37Eleonora Aronica38Jacek Jaworski39David J. Kwiatkowski40Proteome Factory AGTransition Technologies ScienceAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam NeuroscienceDepartment of Medicine, Brigham and Women’s HospitalDepartment of Medicine, Brigham and Women’s HospitalDepartment of Medicine, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical CenterChild Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata UniversityDiagnose- und Behandlungszentrum für Kinder, Vivantes-Klinikum NeuköllnDepartment of Child Neurology, Charité University Medicine BerlinNeurosciences Unit, Queensland Children’s HospitalEpilepsy Service, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Member of ERN EpiCAREEpilepsy Service, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Member of ERN EpiCAREDepartment of Paediatric Neurology, Motol University Hospital, 2nd Medical Faculty, Charles UniversityDepartment of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker–Enfants Malades Hospital, Université Paris cité, Imagine InstituteNeurogenetics Research Group, Vrije Universiteit BrusselDepartment of Paediatric Neurology, Motol University Hospital, 2nd Medical Faculty, Charles UniversityAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam NeuroscienceDepartment. of Pathology and Molecular Medicine, Motol University Hospital, 2nd Medical Faculty, Charles UniversityDepartment of Internal MedicineAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam NeuroscienceAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam NeuroscienceAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam NeuroscienceDepartment of Development and Regeneration Section Pediatric Neurology, University Hospitals KU LeuvenChild Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata UniversityDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteDepartment of Child Neurology, Brain Center University Medical Center UtrechtGenomeScanDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteInternational Institute of Molecular and Cell BiologyGenomeScanTransition Technologies ScienceTransition Technologies ScienceDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteDepartment of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health InstituteProteome Factory AGAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam NeuroscienceInternational Institute of Molecular and Cell BiologyDepartment of Medicine, Brigham and Women’s HospitalAbstract We 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.https://doi.org/10.1038/s41467-023-42855-6 |
| spellingShingle | Franz Huschner Jagoda Głowacka-Walas James D. Mills Katarzyna Klonowska Kathryn Lasseter John M. Asara Romina Moavero Christoph Hertzberg Bernhard Weschke Kate Riney Martha Feucht Theresa Scholl Pavel Krsek Rima Nabbout Anna C. Jansen Bořivoj Petrák Jackelien van Scheppingen Josef Zamecnik Anand Iyer Jasper J. Anink Angelika Mühlebner Caroline Mijnsbergen Lieven Lagae Paolo Curatolo Julita Borkowska Krzysztof Sadowski Dorota Domańska-Pakieła Magdalena Blazejczyk Floor E. Jansen Stef Janson Malgorzata Urbanska Aleksandra Tempes Bart Janssen Kamil Sijko Konrad Wojdan Sergiusz Jozwiak Katarzyna Kotulska Karola Lehmann Eleonora Aronica Jacek Jaworski David J. Kwiatkowski Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years Nature Communications |
| title | Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years |
| title_full | Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years |
| title_fullStr | Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years |
| title_full_unstemmed | Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years |
| title_short | Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years |
| title_sort | molecular epistop a comprehensive multi omic analysis of blood from tuberous sclerosis complex infants age birth to two years |
| url | https://doi.org/10.1038/s41467-023-42855-6 |
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