PXD033987

PXD033987 is an original dataset announced via ProteomeXchange.

Title	An integrated multi-omic network analysis identifies seizure-associated dysregulated pathways in the GAERS model of absence epilepsy
Description	Absence epilepsy syndromes are part of the genetic generalized epilepsies, the pathogenesis of which remains poorly understood, although a polygenic architecture is presumed. Current focus on single molecule or gene identification to elucidate epileptogenic drivers is unable to fully cap-ture the complex dysfunctional interactions occurring at a genetic/proteomic/metabolomic level. Here, we employ a multi-omic, network-based approach to characterize the molecular signature associated with absence epilepsy-like phenotype seen in a well validated rat model of genetic generalized epilepsy with absence seizures. Electroencephalographic and behavioral data was collected from Genetic Absence Epilepsy Rats from Strasbourg (GAERS, n=6) and non-epileptic controls (NEC, n=6), followed by proteomic and metabolomic profiling of the cortical and tha-lamic tissue of rats from both groups. The general framework of weighted correlation network analysis was used to identify groups of highly correlated proteins and metabolites, which were then functionally annotated through joint pathway enrichment analysis. In both brain regions a large protein-metabolite module was found to be highly associated with the GAERS strain, ab-sence seizures and associated anxiety and depressive-like phenotype. Quantitative pathway analysis indicated enrichment in oxidative pathways and a downregulation of the lysine degra-dation pathway in both brain regions. GSTM1 and ALDH2 were identified as central regulatory hubs of the seizure-associated module in the somatosensory cortex and thalamus, respectively. These enzymes are involved in lysine degradation and play important roles in maintaining oxi-dative balance. We conclude that the dysregulated pathways identified in the seizure-associated module may be involved in the aetiology and maintenance of absence seizure activity. This dysregulated activity could potentially be modulated by targeting one or both central regulatory hubs.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_05:20:36.515.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Rattus rattus (Black rat); NCBI TaxID: 10117;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-19 02:26:23	ID requested
⏵ 1	2022-08-11 05:20:37	announced

Harutyunyan A, Chong D, Li R, Shah AD, Ali Z, Huang C, Barlow CK, Perucca P, O'Brien TJ, Jones NC, Schittenhelm RB, Anderson A, Casillas-Espinosa PM, An Integrated Multi-Omic Network Analysis Identifies Seizure-Associated Dysregulated Pathways in the GAERS Model of Absence Epilepsy. Int J Mol Sci, 23(11):(2022) [pubmed]

submitter keyword: An integrated multi-omic network analysis identifies sei-zure-associated dysregulated pathways in the GAERS model of absence epilepsy

Pablo Casillas-Espinosa
contact affiliation	Department of Medicine (The Royal Melbourne Hospital), The University of Melbourne, 3000, Victoria, Australia. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, 3004, Victoria, Australia.
contact email	pablo.casillas-espinosa@monash.edu
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD033987

PRIDE project URI

• PRIDE
  1. PXD033987
     1. Label: PRIDE project
     2. Name: An integrated multi-omic network analysis identifies seizure-associated dysregulated pathways in the GAERS model of absence epilepsy