Semantic similarity. The phenotype era in the epilepsies has now officially started. While it is possible for us to generate and analyze genetic data in the epilepsies at scale, phenotyping typically remains a manual, non-scalable task. This contrast has resulted in a significant imbalance where it is often easier to obtain genomic data than clinical data. However, it is often not the lack of clinical data that causes this problem, but our ability to handle it. Clinical data is often unstructured, incomplete and multi-dimensional, resulting in difficulties when trying to meaningfully analyze this information. Today, our publication on analyzing more than 31,000 phenotypic terms in 846 patient-parent trios with developmental and epileptic encephalopathies (DEE) appeared online. We developed a range of new concepts and techniques to analyze phenotypic information at scale, identified previously unknown patterns, and were bold enough to challenge the prevailing paradigms on how statistical evidence for disease causation is generated. Continue reading
Monthly Archives: August 2020
Copy Number Variations in the epilepsies – a 2020 update
CNV. There are different forms of genetic variation and historically, our ability to query the entire exome or genome is a relatively recent development. However, the first type of genetic variation that could be assessed in the epilepsies in large cohorts were copy number variations (CNV), small gains or losses of chromosomal materials. In a recent study, the entire Epi25 cohort was analyzed for CNVs, giving a long-needed update on the role of the structural genomic variations in various forms of epilepsies and highlighting that the overall landscape of CNVs in the epilepsies is well understood and delineated. With up to 3% of individuals with epilepsies carrying some of the recurrent CNVs, this type of genomic variation remains a rare, but important source of genetic morbidity in the epilepsies. Continue reading
The natural history of genetic epilepsies as told by 3,200 years of electronic medical records
EMR. When we consider the natural history of rare diseases like the genetic epilepsies, we typically think about a lack of longitudinal data that contrasts with the abundant genetic information that is available nowadays – the so-called phenotyping gap. We typically suggest that we need to obtain this information in future prospective studies to better understand long-term outcome, response to medications, and potential early warning signs for an adverse disease course. However, a vast amount of clinical data is collected on an ongoing basis through electronic medical records (EMR) as a byproduct of regular patient care. In a recent study, our group built tools to mine the electronic medical records to assess the disease history of 658 individuals with known or presumed epilepsies using clinical information collected at more than 62,000 patients encounters across more than 3,200 patient years. Here is a brief summary of our first study on EMR genomics, an untapped resource that has the potential to improve our understanding of the genetic epilepsies. Continue reading
