| Autor: |
Dwivedi AK; Institute for Molecular Medicine, University of Southern Denmark, Odense M, Denmark., Mahesh A; Institute for Molecular Medicine, University of Southern Denmark, Odense M, Denmark., Sanfeliu A; FutureNeuro SFI Research Centre, RCSI University of Medicine & Health Sciences, Dublin, Ireland., Larkin J; FutureNeuro SFI Research Centre, RCSI University of Medicine & Health Sciences, Dublin, Ireland., Siwicki RA; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland., Sweeney KJ; FutureNeuro SFI Research Centre, RCSI University of Medicine & Health Sciences, Dublin, Ireland., O'Brien DF; FutureNeuro SFI Research Centre, RCSI University of Medicine & Health Sciences, Dublin, Ireland., Widdess-Walsh P; FutureNeuro SFI Research Centre, RCSI University of Medicine & Health Sciences, Dublin, Ireland., Picelli S; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland., Henshall DC; FutureNeuro SFI Research Centre, RCSI University of Medicine & Health Sciences, Dublin, Ireland., Tiwari VK; Institute for Molecular Medicine, University of Southern Denmark, Odense M, Denmark. |
| Abstrakt: |
The availability and integration of electrophysiological and molecular data from the living brain is critical to understand and diagnose complex human disease. Intracranial stereo electroencephalography (SEEG) electrodes used for identifying the seizure focus on epilepsy patients could enable the integration of such multimodal data. Here, we report MoPEDE (Multimodal Profiling of Epileptic Brain Activity via Explanted Depth Electrodes), a method that recovers extensive protein-coding transcripts, including cell-type markers, DNA methylation and short variant profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function. We find gene expression gradients that correspond with the neurophysiology-assigned epileptogenicity index but also outlier molecular fingerprints in some electrodes, potentially indicating seizure generation or propagation zones not detected during electroclinical assessments. Additionally, we identify DNA methylation profiles indicative of transcriptionally permissive or restrictive chromatin states and SEEG-adherent differentially expressed and methylated genes not previously associated with epilepsy. Together, these findings validate that RNA profiles and genome-wide epigenetic data from explanted SEEG electrodes offer high-resolution surrogate molecular landscapes of brain activity. The MoPEDE approach has the potential to enhance diagnostic decisions and deepen our understanding of epileptogenic network processes in the human brain. |
