Print Email Facebook Twitter Predicting variant deleteriousness in non-human species Title Predicting variant deleteriousness in non-human species: Applying the CADD approach in mouse Author Groß, C. (TU Delft Pattern Recognition and Bioinformatics; Wageningen University & Research) de Ridder, D. (Wageningen University & Research) Reinders, M.J.T. (TU Delft Pattern Recognition and Bioinformatics) Date 2018 Abstract Background: Predicting the deleteriousness of observed genomic variants has taken a step forward with the introduction of the Combined Annotation Dependent Depletion (CADD) approach, which trains a classifier on the wealth of available human genomic information. This raises the question whether it can be done with less data for non-human species. Here, we investigate the prerequisites to construct a CADD-based model for a non-human species. Results: Performance of the mouse model is competitive with that of the human CADD model and better than established methods like PhastCons conservation scores and SIFT. Like in the human case, performance varies for different genomic regions and is best for coding regions. We also show the benefits of generating a species-specific model over lifting variants to a different species or applying a generic model. With fewer genomic annotations, performance on the test set as well as on the three validation sets is still good. Conclusions: It is feasible to construct species-specific CADD models even when annotations such as epigenetic markers are not available. The minimal requirement for these models is the availability of a set of genomes of closely related species that can be used to infer an ancestor genome and substitution rates for the data generation. Subject Genome annotationGenomicsMouse geneticsSequence annotationVariant annotationOA-Fund TU Delft To reference this document use: http://resolver.tudelft.nl/uuid:b6be779e-7e0c-4b06-ac3e-56c287bbeb8f DOI https://doi.org/10.1186/s12859-018-2337-5 ISSN 1471-2105 Source BMC Bioinformatics, 19 (1), 1-10 Part of collection Institutional Repository Document type journal article Rights © 2018 C. Groß, D. de Ridder, M.J.T. Reinders Files PDF 47408262_s12859_018_2337_5.pdf 1.22 MB Close viewer /islandora/object/uuid:b6be779e-7e0c-4b06-ac3e-56c287bbeb8f/datastream/OBJ/view