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Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

Author

Listed:
  • Franz Huschner

    (Proteome Factory AG)

  • Jagoda Głowacka-Walas

    (Transition Technologies Science
    Warsaw University of Technology, The Institute of Computer Science)

  • James D. Mills

    (Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
    UCL Queen Square Institute of Neurology
    Chalfont Centre for Epilepsy)

  • Katarzyna Klonowska

    (Brigham and Women’s Hospital)

  • Kathryn Lasseter

    (Brigham and Women’s Hospital)

  • John M. Asara

    (Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center)

  • Romina Moavero

    (Tor Vergata University
    Bambino Gesù Children’s Hospital, IRCCS)

  • Christoph Hertzberg

    (Vivantes-Klinikum Neukölln)

  • Bernhard Weschke

    (Charité University Medicine Berlin)

  • Kate Riney

    (Queensland Children’s Hospital
    School of Medicine, University of Queensland)

  • Martha Feucht

    (Medical University of Vienna, Member of ERN EpiCARE)

  • Theresa Scholl

    (Medical University of Vienna, Member of ERN EpiCARE)

  • Pavel Krsek

    (Department of Paediatric Neurology, Motol University Hospital, 2nd Medical Faculty, Charles University)

  • Rima Nabbout

    (Université Paris cité, Imagine Institute)

  • Anna C. Jansen

    (Vrije Universiteit Brussel)

  • Bořivoj Petrák

    (Department of Paediatric Neurology, Motol University Hospital, 2nd Medical Faculty, Charles University)

  • Jackelien Scheppingen

    (Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience)

  • Josef Zamecnik

    (Motol University Hospital, 2nd Medical Faculty, Charles University)

  • Anand Iyer

    (Department of Internal Medicine)

  • Jasper J. Anink

    (Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience)

  • Angelika Mühlebner

    (Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
    University Medical Center Utrecht)

  • Caroline Mijnsbergen

    (Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience)

  • Lieven Lagae

    (University Hospitals KU Leuven)

  • Paolo Curatolo

    (Tor Vergata University)

  • Julita Borkowska

    (The Children’s Memorial Health Institute)

  • Krzysztof Sadowski

    (The Children’s Memorial Health Institute)

  • Dorota Domańska-Pakieła

    (The Children’s Memorial Health Institute)

  • Magdalena Blazejczyk

    (The Children’s Memorial Health Institute)

  • Floor E. Jansen

    (Brain Center University Medical Center Utrecht)

  • Stef Janson

    (GenomeScan)

  • Malgorzata Urbanska

    (The Children’s Memorial Health Institute)

  • Aleksandra Tempes

    (International Institute of Molecular and Cell Biology)

  • Bart Janssen

    (GenomeScan)

  • Kamil Sijko

    (Transition Technologies Science)

  • Konrad Wojdan

    (Transition Technologies Science
    Warsaw University of Technology, Institute of Heat Engineering)

  • Sergiusz Jozwiak

    (The Children’s Memorial Health Institute
    Medical University of Warsaw)

  • Katarzyna Kotulska

    (The Children’s Memorial Health Institute)

  • Karola Lehmann

    (Proteome Factory AG)

  • Eleonora Aronica

    (Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
    Heemstede the Netherlands)

  • Jacek Jaworski

    (International Institute of Molecular and Cell Biology)

  • David J. Kwiatkowski

    (Brigham and Women’s Hospital)

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.

Suggested Citation

  • 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 , 2023. "Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42855-6
    DOI: 10.1038/s41467-023-42855-6
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