Annotation of the functional impact of coding genetic variants

Abstract

Summary. Coding genetic variants can have profound effects on protein function. Computational tools for the prediction of these effects are used to complement and guide experimental biological studies. Phylogenetic analyses that determine the evolutionary relationship among related sequences are commonly used to distinguish between functionally significant and insignificant gene variations. Here, we have reviewed applications of the non-alignment sequence analyses method for phylogenetic analyses, ISTREE. Furthermore, we assessed how an unsupervised ISTREE-d3 method based on the universal d3 measure responds to this task compared to supervised and semi-supervised ISTREE methods that were previously used in two studies. The findings presented here suggest that ISTREE-d3 can efficiently substitute for the corresponding supervised models, given that it is more suitable for automatic applications. In conclusion, the ISTREE-d3 method has a broad biological relevance and represents a promising approach in functional assessment of coding gene variations.