CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
Exploring Human Variation and its impact on proteins and in the Clinic
Janet Thornton1, Roman Laskowski1, James Stephenson1
1European Bioinformatics Institute (EMBL-EBI)
Genome sequencing has opened up the possibility of exploring the genetic basis of human evolution and the differences between individuals. Using computational methods and 3D protein structures, we compared disease associated variants with ‘natural’ variants observed in 1000 human genomes, showing significant differences in their distributions. Many of the mutations that most often cause diseases were the least frequently observed ‘natural’ variants. Recently we have been exploring how protein domain information can help in the interpretation of the effects of non-synonymous mutations, especially from a structural perspective. We observe that the ‘equivalent’ mutation in the same domain family but in different proteins, can have very different consequences, depending on the context in which it occurs. In collaboration with the Deciphering Developmental Disorders Consortium, we have shown how recurrent variants can disrupt protein structures and ultimately cause the observed rare diseases. The 100,000 genomes project, funded by the UK government through the NHS, provides a stimulus to bring this new technology into the clinic. This brings both challenges and great opportunities. One of the major challenges is handling the scale and interpreting the complexity of genomic data. In this talk I will describe how the data landscape in biology has changed, drawing on my experiences at the European Bioinformatics Institute and with ELIXIR, which provides many of the core biomolecular data resources used worldwide. The changes in the medical data landscape are still emerging and have a long way to go, but the prospect of ‘combining’ the molecular data with the medical phenotypic data offers great hope for improved diagnoses and therapies for the future.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.