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

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

doi:10.1038/s41467-023-42855-6

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

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 AninkAngelika 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	7664
Number of pages	15
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-42855-6
Publication status	Published - Dec 2023

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Huschner, F., Głowacka-Walas, J., Mills, J. D., Klonowska, K., Lasseter, K., Asara, J. M., Moavero, R., Hertzberg, C., Weschke, B., Riney, K., Feucht, M., Scholl, T., Krsek, P., Nabbout, R., Jansen, A. C., Petrák, B., van Scheppingen, J., Zamecnik, J., Iyer, A., ... Kwiatkowski, D. J. (2023). Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years. Nature Communications, 14(1), Article 7664. https://doi.org/10.1038/s41467-023-42855-6

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title = "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 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.",

author = "Franz Huschner and Jagoda G{\l}owacka-Walas and Mills, {James D} and Katarzyna Klonowska and Kathryn Lasseter and Asara, {John M} and Romina Moavero and Christoph Hertzberg and Bernhard Weschke and Kate Riney and Martha Feucht and Theresa Scholl and Pavel Krsek and Rima Nabbout and Jansen, {Anna C} and Bo{\v r}ivoj Petr{\'a}k and {van Scheppingen}, Jackelien and Josef Zamecnik and Anand Iyer and Anink, {Jasper J} and Angelika M{\"u}hlebner and Caroline Mijnsbergen and Lieven Lagae and Paolo Curatolo and Julita Borkowska and Krzysztof Sadowski and Dorota Doma{\'n}ska-Pakie{\l}a and Magdalena Blazejczyk and Jansen, {Floor E} and Stef Janson and Malgorzata Urbanska and Aleksandra Tempes and Bart Janssen and Kamil Sijko and Konrad Wojdan and Sergiusz Jozwiak and Katarzyna Kotulska and Karola Lehmann and Eleonora Aronica and Jacek Jaworski and Kwiatkowski, {David J}",

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year = "2023",

month = dec,

doi = "10.1038/s41467-023-42855-6",

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Huschner, F, Głowacka-Walas, J, Mills, JD, Klonowska, K, Lasseter, K, Asara, JM, Moavero, R, Hertzberg, C, Weschke, B, Riney, K, Feucht, M, Scholl, T, Krsek, P, Nabbout, R, Jansen, AC, Petrák, B, van Scheppingen, J, Zamecnik, J, Iyer, A, Anink, JJ, Mühlebner, A, Mijnsbergen, C, Lagae, L, Curatolo, P, Borkowska, J, Sadowski, K, Domańska-Pakieła, D, Blazejczyk, M, Jansen, FE, Janson, S, Urbanska, M, Tempes, A, Janssen, B, Sijko, K, Wojdan, K, Jozwiak, S, Kotulska, K, Lehmann, K, Aronica, E, Jaworski, J & Kwiatkowski, DJ 2023, 'Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years', Nature Communications, vol. 14, no. 1, 7664. https://doi.org/10.1038/s41467-023-42855-6

TY - JOUR

T1 - Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

AU - Huschner, Franz

AU - Głowacka-Walas, Jagoda

AU - Mills, James D

AU - Klonowska, Katarzyna

AU - Lasseter, Kathryn

AU - Asara, John M

AU - Moavero, Romina

AU - Hertzberg, Christoph

AU - Weschke, Bernhard

AU - Riney, Kate

AU - Feucht, Martha

AU - Scholl, Theresa

AU - Krsek, Pavel

AU - Nabbout, Rima

AU - Jansen, Anna C

AU - Petrák, Bořivoj

AU - van Scheppingen, Jackelien

AU - Zamecnik, Josef

AU - Iyer, Anand

AU - Anink, Jasper J

AU - Mühlebner, Angelika

AU - Mijnsbergen, Caroline

AU - Lagae, Lieven

AU - Curatolo, Paolo

AU - Borkowska, Julita

AU - Sadowski, Krzysztof

AU - Domańska-Pakieła, Dorota

AU - Blazejczyk, Magdalena

AU - Jansen, Floor E

AU - Janson, Stef

AU - Urbanska, Malgorzata

AU - Tempes, Aleksandra

AU - Janssen, Bart

AU - Sijko, Kamil

AU - Wojdan, Konrad

AU - Jozwiak, Sergiusz

AU - Kotulska, Katarzyna

AU - Lehmann, Karola

AU - Aronica, Eleonora

AU - Jaworski, Jacek

AU - Kwiatkowski, David J

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-023-42855-6

DO - 10.1038/s41467-023-42855-6

M3 - Article

C2 - 37996417

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7664

ER -

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

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