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

被引：5

作者：

Huschner, Franz ^{[1
]}

Glowacka-Walas, Jagoda ^{[2
,3
]}

Mills, James D. ^{[4
,5
,6
]}

Klonowska, Katarzyna ^{[7
]}

Lasseter, Kathryn ^{[7
]}

Asara, John M. ^{[8
,9
]}

Moavero, Romina ^{[10
,11
]}

Hertzberg, Christoph ^{[12
]}

Weschke, Bernhard ^{[13
]}

Riney, Kate ^{[14
,15
]}

Feucht, Martha ^{[16
]}

Scholl, Theresa ^{[16
]}

Krsek, Pavel ^{[17
]}

Nabbout, Rima ^{[18
]}

Jansen, Anna C. ^{[19
]}

Petrak, Borivoj ^{[17
]}

van Scheppingen, Jackelien ^{[4
]}

Zamecnik, Josef ^{[20
]}

Iyer, Anand ^{[21
]}

Anink, Jasper J. ^{[4
]}

Muehlebner, Angelika ^{[4
,22
]}

Mijnsbergen, Caroline ^{[4
]}

Lagae, Lieven ^{[23
]}

Curatolo, Paolo ^{[10
]}

Borkowska, Julita ^{[24
]}

Sadowski, Krzysztof ^{[24
]}

Domanska-Pakiela, Dorota ^{[24
]}

Blazejczyk, Magdalena ^{[24
]}

Jansen, Floor E. ^{[25
]}

Janson, Stef ^{[26
]}

Urbanska, Malgorzata ^{[24
]}

Tempes, Aleksandra ^{[27
]}

Janssen, Bart ^{[26
]}

Sijko, Kamil ^{[2
]}

Wojdan, Konrad ^{[2
,28
]}

Jozwiak, Sergiusz ^{[24
,29
]}

Kotulska, Katarzyna ^{[24
]}

Lehmann, Karola ^{[1
]}

Aronica, Eleonora ^{[4
,30
]}

Jaworski, Jacek ^{[27
]}

Kwiatkowski, David J. ^{[7
]}

机构：

[1] Proteome Factory AG, Berlin, Germany

[2] Transit Technol Sci, Warsaw, Poland

[3] Warsaw Univ Technol, Inst Comp Sci, Warsaw, Poland

[4] Univ Amsterdam, Dept Neuro Pathol, Amsterdam UMC, Amsterdam Neurosci, Amsterdam, Netherlands

[5] UCL Queen Sq Inst Neurol, Dept Clin & Expt Epilepsy, London, England

[6] Chalfont Ctr Epilepsy, Gerrards Cross, England

[7] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[8] Harvard Med Sch, Dept Med, Boston, MA USA

[9] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA USA

[10] Tor Vergata Univ, Syst Med Dept, Child Neurol & Psychiat Unit, Rome, Italy

[11] IRCCS, Bambino Gesu Childrens Hosp, Dev Neurol, Rome, Italy

[12] Vivantes Klinikum Neukolln, Diag & Behandlungszentrum Kinder, Berlin, Germany

[13] Charite Univ Med Berlin, Dept Child Neurol, Berlin, Germany

[14] Queensland Childrens Hosp, Neurosci Unit, South Brisbane, Qld, Australia

[15] Univ Queensland, Sch Med, St Lucia, Qld, Australia

[16] Med Univ Vienna, Dept Pediat & Adolescent Med, Epilepsy Serv, ERN EpiCARE, Vienna, Austria

[17] Charles Univ Prague, Motol Univ Hosp, Med Fac 2, Dept Paediat Neurol, Prague, Czech Republic

[18] Univ Paris Cite, Necker Enfants Malad Univ Hosp, Dept Pediat Neurol, Reference Ctr Rare Epilepsies,Imagine Inst, Paris, France

[19] Vrije Univ Brussel, Neurogenet Res Grp, Brussels, Belgium

[20] Charles Univ Prague, Motol Univ Hosp, Med Fac 2, Dept Pathol & Mol Med, Prague, Czech Republic

[21] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[22] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[23] Univ Hosp KU Leuven, Dept Dev, Regenerat Sect Pediat Neurol, Leuven, Belgium

[24] Childrens Mem Hlth Inst, Dept Neurol & Epileptol, ERN EPICARE, Warsaw, Poland

[25] Univ Med Ctr Utrecht, Brain Ctr, Dept Child Neurol, Utrecht, Netherlands

[26] GenomeScan, Leiden, Netherlands

[27] Int Inst Mol & Cell Biol, Warsaw, Poland

[28] Warsaw Univ Technol, Inst Heat Engn, Warsaw, Poland

[29] Med Univ Warsaw, Dept Child Neurol, Warsaw, Poland

[30] Stichting Epilepsie Instellingen Nederland SEIN, Utrecht, Netherlands

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

关键词：

R/BIOCONDUCTOR PACKAGE; EXPRESSION ANALYSIS; VIGABATRIN; EPILEPSY; GENE; BIOCONDUCTOR; PLATFORM;

D O I：

10.1038/s41467-023-42855-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. A comprehensive multi-omic analysis of the EPISTOP trial for Tuberous Sclerosis Complex (TSC). was performed. Here, authors show many differences in serum proteins and metabolites, and blood RNA species, including associations with seizure development.

引用

页数：15

共 3 条

[1] Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study
Moavero, Romina
Benvenuto, Arianna
Gialloreti, Leonardo Emberti
Siracusano, Martina
Kotulska, Katarzyna
Weschke, Bernhard
Riney, Kate
Jansen, Floor E.
Feucht, Martha
Krsek, Pavel
Nabbout, Rima
Jansen, Anna C.
Wojdan, Konrad
Borkowska, Julita
Sadowski, Krzystof
Hertzberg, Christoph
Hulshof, Hanna
Samueli, Sharon
Benova, Barbora
Aronica, Eleonora
Kwiatkowski, David J.
Lagae, Lieven
Jozwiak, Sergiusz
Curatolo, Paolo
Anink, J.
Blazejczyk, M.
Bongaerts, A.
Borkowska, J.
Breuillard, D.
Chmielewski, D.
Dabrowska, M.
De Ridder, J.
Giannikou, K.
Glowacka, J.
Hamieh, L.
Harvza, A.
Iyer, A.
Janssen, Bart
Jaworski, J.
Kaczorowska-Frontczak, M.
Lehmann, K.
Leusman, A.
Madcowiak, N.
Mills, J.
Muelebner, A.
Scheldeman, C.
Sciuto, A.
Sijko, K.
Slowinska, M.
Tempes, A.
JOURNAL OF CLINICAL MEDICINE, 2019, 8 (06)
[2] Safety of Sirolimus in Patients with Tuberous Sclerosis Complex under Two Years of Age-A Bicenter Retrospective Study
Smialek, Dominika
Jozwiak, Sergiusz
Kotulska, Katarzyna
JOURNAL OF CLINICAL MEDICINE, 2023, 12 (01)
[3] Efficacy and Safety of Adjunctive Everolimus for Treatment-Refractory Seizures Associated With Tuberous Sclerosis Complex (TSC) in Children Under 6 Years of Age: Results From the Phase 3 EXIST-3 Extension Phase
Franz, D.
Lawson, J.
Yapici, Z.
Ikeda, H.
Polster, T.
Nabbout, R.
Curatolo, P.
de Vries, P.
Dlugos, D.
Fan, J.
Louveau, A.
Pelov, D.
Voi, M.
French, J.
ANNALS OF NEUROLOGY, 2017, 82 : S282 - S282

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