Node leaders: Gonzalo Nido and Dimitrios Kleftogiannis
Dr. Gonzalo Nido is a senior researcher in bioinformatics at the University of Bergen, with more than a decade of experience in the analysis of multiomic datasets, including genomics, epigenomics, transcriptomics, and proteomics, as well as single-cell omics, and data integration. His work has made important advances particularly in the field of Parkinson’s disease transcriptomics.
Dr. Dimitrios Kleftogiannis is a senior bioinformatician at the University of Bergen. His work focuses on the development and application of computational approaches to dissect omics datasets from Next Generation Sequencing (NGS), as well as mass cytometry (CyTOF) and imaging mass cytometry (IMC) technologies. He is also interested in the application of machine learning for biomarker discoveries in multiple
sclerosis.
Node activities
The concept of systems medicine in neurology is the backbone of the Centre. Based on the wealth of data collected through the clinical and translational activities of the Centre, and using supervised and unsupervised data-analysis models, including artificial intelligence (AI), the node is developing specific and sensitive biomarker systems to enable and refine early and precise diagnosis, stratification, and prediction of treatment response. Our Parkinson’s disease (PD) team has jump-started this activity and is paving the way for the other diseases to follow.
During 2023, the Systems Biology & Bioinformatics (SBB) Node made substantial advances:
The ParkOme initiative integrates state-of-the-art multiomics and clinicopathological data, with the aim to advance the mechanistic understanding of PD (and subtypes thereof), and to discover novel biomarkers and treatment targets. To this end, the SBB Node is mapping the genome, epigenome, transcriptome, proteome, and metabolome of multiple tissues from individuals with neurodegenerative parkinsonisms and healthy controls. To mitigate the confounder of cellular heterogeneity, they are conducting additional studies in single cells using a dual strategy: 1) Highthroughput single-cell analyses, using the inhouse 10X Genomics platform. 2) Pathology-guided single-cell transcriptomics to elucidate the selective neuronal vulnerability to PD-associated pathology (e.g., as α-synuclein aggregation, or mitochondrial dysfunction). Integration across omics layers and with clinical, pathology, environmental and epidemiological information, enables the team to identify complex molecular interactions, and how these interact with the environment and, in turn, influence the disease phenotype. Molecular signatures emerging from this work are translated into disease models by the Cell Models
Node, therapeutic targets by the Drug Discovery Node, as well as candidate biomarkers for disease diagnosis and stratification, which are tested in the STRAT-PARK cohort.
Funding was in 2023 secured for the The Mito-ALS study, investigating mechanisms of cell death in ALS, using pathologic material from the brain banks in Barcelona and the Netherlands. The aim is to study whether complex 1 deficiency is present in ALS.
Several key milestones were reached in 2023. The transcriptome and coding genome sequence of more than 1,300 brain samples were analysed to completion. This constitutes by far the largest transcriptomic repository of neurodegenerative parkinsonism’s in the world, including PD, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, dementia with Lewy bodies, Alzheimer’s disease, and healthy controls. In addition, we mapped and analysed the proteome of ~500 of the same samples, and singlenucleus transcriptomics using the 10X Genomics technology in 50 individuals. These analyses have revealed multiple novel molecular signatures which characterise neurodegenerative parkinsonism – both associated with and independent of the severity of the proteinopathy – at the level of individual genes/proteins and molecular processes and pathways.
This data has constituted the foundation for several original papers, currently in review or revision in high-impact journals, including Molecular Neurodegeneration and Nature Neuroscience. Moreover, these findings have been presented in several international conferences generation significant interest in the reported discoveries.