Nieuwe technologieën en bioinformatica toegepast op moleculair genetisch onderzoek van neurodegeneratieve hersenziekten
18 december 2018
UAntwerpen, Campus Drie Eiken, Gebouw Q, Promotiezaal - Universiteitsplein 1 - 2610 Wilrijk (Antwerpen) (route: UAntwerpen, Campus Drie Eiken
16 - 18 uur
Wouter De Coster
Christine Van Broeckhoven
Doctoraatsverdediging Wouter De Coster - Departement Biomedische Wetenschappen
Neurodegenerative diseases such as Alzheimer Disease and Frontotemporal Dementia are an increasing burden on patients and caregivers in an aging society. No therapeutic approaches are currently available to halt or slow down the progressive neuronal death and the accompanying loss of cognitive functions. Genetic research has the potential to identify key factors contributing to the early stages of these complex disorders, as such leading to targets potentially suitable for therapeutics.
As thousands of structural variants per genome are missed using currently dominant short read sequencing technologies we are employing single-molecule long read sequencing on the PromethION device. As new technologies also require new bioinformatic approaches I have developed a widely-used software package for quality assessment, visualization, and processing of the obtained data. Furthermore, I have assessed the performance of the currently available software for alignment and structural variant calling in a well-characterized human genome, critically informing us about the accuracy of this technology and best recommendations for tools for future projects, as well as identifying scenarios in which the current tools are suboptimal.
We have also evaluated long read genome sequencing for genotyping of expanded tandem repeats, a challenging large inversion and the inference of methylation status of a locus, haplotype or single molecules. As such we take the first steps to a more complete assessment of human genomic variation in health and disease. I conclude by sketching the way forward for a complete and unbiased characterization of human genomes.