Project description:Genome-wide methylation profiling on 15 Father-Mother-Offspring trios with Genetic Generalized Epilepsies. All trios have 2 affected (1 parent and offspring) and 1 healthy individuals. Illumina HumanMethylation450 BeadChip was used to obtain DNA methylation profiles which has probes for aproximetely 450000 CpG loci.
Project description:We used NGS on a cohort of complex genetics sarcomas to study their transcriptomes (RNA-seq technology), looking for recurrent and specific gene fusions. We identified multiple TRIO fusions with different partners in our cohort. No TRIO fusions were reported in negative-control cells (normal tissues) and in simple genetics sarcomas.
Project description:Purpose Identification of potential biomarkers of seizures. Methods In this exploratory study, we quantified plasma protein intensities in 15 patients with recent seizures compared to 15 patients with long-standing seizure freedom. Using TMT-based proteomics we found fifty-one differentially expressed proteins. Results Network analyses including co-expression networks and protein-protein interaction networks, using the STRING database, followed by network centrality and modularity analyses revealed 22 protein modules, with one module showing a significant association with seizures. The protein-protein interaction network centered around this module identified a subnetwork of 125 proteins, grouped into four clusters. Notably, one cluster (mainly enriching inflammatory pathways and Gene Ontology terms) demonstrated the highest enrichment of known epilepsy-related genes. Conclusion Overall, our network-based approach identified a protein module linked with seizures. The module contained known markers of epilepsy and inflammation. The results also demonstrate the potential of network analysis in discovering new biomarkers for improved epilepsy management.
Project description:DNA methylation profiling has emerged as a valuable tool for tumor classification, exemplified by the German Cancer Research Center's creation of online classifiers for CNS tumors and sarcomas. Identification of rare molecular events, such as TRIO::TERT fusion in undifferentiated sarcomas, through DNA methylation profiling and transcriptome analysis aims to define distinct molecular subgroups within sarcomas of uncertain diagnosis, potentially improving classification and treatment strategies.In this study, we present 8 cases of sarcomas characterized by TRIO::TERT fusion, establishing it as a distinct molecular subtype of sarcomas. This fusion represents a consistent molecular feature across all analyzed tumors, suggesting its pivotal role in sarcomatogenesis. Identifying TRIO::TERT transcript sarcoma as a new tumor type may enhance diagnostic strategies for improved patient management.
Project description:Genetic generalized epilepsies (GGE) are genetically determined, as their name implies and they are clinically characterized by generalized seizures involving both sides of the brain in the absence of detectable brain lesions or other known causes. GGEs are yet complex and are influenced by many different genetic and environmental factors. Methylation specific epigenetic marks are one of the players of the complex epileptogenesis scenario leading to GGE. In this study, we have set out to perform genome-wide methylation profiling to analyze GGE trios each consisting of an affected parent-offspring couple along with an unaffected parent. We have developed a novel scoring scheme within trios to categorize each locus analyzed as hypo or hypermethylated. This stringent approach classified differentially methylated genes in each trio and helped us to produce trio specific and pooled gene lists with inherited and aberrant methylation levels. In order to analyze the methylation differences from a boarder perspective, we performed enrichment analysis with these lists using the PANOGA software. This collective effort has led us to detect pathways associated with the GGE phenotype, including the neurotrophin signaling pathway. We have demonstrated a trio based approach to genome-wide DNA methylation analysis that identified individual and possibly minor changes in methylation marks that could be involved in epileptogenesis leading to GGE.
Project description:This SuperSeries is composed of the following subset Series: GSE27015: Rat model of MTLE: Animals with epilepsy vs animals without epilepsy (Agilent) GSE27166: Rat model of MTLE: Animals with epilepsy vs animals without epilepsy (codelink) Refer to individual Series