Measuring Variant Conservation with GERP Score and Siphy

The more annotations, the better! We've recently added 2 new annotations to assist with variant prioritisation as a measure of variant conservation and these are GERP scores and Siphy. GERP stands for Genomic Evolutionary Rate Profiling. Conceptually, GERP is a method for the identification of slowly evolving regions in a multiple sequence alignment, defined as ‘constrained elements’. "Constrained elements are identified by comparing the observed to the expected rates of evolution for each window, and defining all those regions whose collective observed rates of evolution are significantly lower than would be expected under a null model." More simply, it is a score used to calculate the conservation of each nucleotide in multi-species alignment with ranges from -12.3 to 6.17, with 6.17 being the most conserved. Positive scores (observed fewer than expected) indicate that a site is under evolutionary constraint. Negative scores may be weak evidence of accelerated rates of evolution. The detailed description can be found in this publication: http://genome.cshlp.org/content/15/7/901.full SiPhy stands for SIte-specific PHYlogenetic analysis. A conservation score that takes the type of mutation into account. SiPhy scores are from dbNSFP, and are on the log odds scale, with most scores ranging between 0 and 20. Higher scores indicate higher conservation. More info can be found here: https://academic.oup.com/bioinformatics/article/25/12/i54/187307 These new annotations are displayed under the 'Latest annotations' tab and are loaded dynamically when the web page loads. Because we don't actually store the information, we can't make them filterable on the search page just yet.