The ParkOme – a multidimensional molecular atlas of PD
We are currently in the process of establishing the ParkOme database, a multidimensional molecular atlas of PD at unprecedented resolution. We are mapping the molecular landscape of PD in key-regions of fresh-frozen post-mortem brain (n > 1,000). In each bulk-tissue sample, we are constructing a multilayer molecular map combining the genome, DNA-methylation, selected histone modifications, chromatin accessibility, transcriptome and proteome. To mitigate the confounder of cellular heterogeneity, we are conducting additional studies in single cells using a dual strategy: 1) High-throughput single-cell analyses, using our 10X Genomics platform. 2) Pathology-guided single-cell transcriptomics to elucidate the selective neuronal vulnerability to PD-associated pathology such as α-synuclein aggregation, mitochondrial or lysosomal dysfunction.
We will interrogate the ParkOme using a combination of powerful supervised and unsupervised computational analyses (including artificial intelligence). Molecular signatures defining PD and its subclasses will be identified and translated into: 1) Disease models recapitulating subclasses of human disease. These will be developed and characterized in our cell model workflow, 2) Precision biomarkers for patient stratification in clinical practice, and 3) Therapeutic targets tailored to the molecular profile of patients. Biomarkers and therapies emerging from this work may trigger clinical studies