KD4v: Comprehensible Knowledge Discovery System for Missense Variant.

A major challenge in the post-genomic era is a better understanding of how human genetic alterations involved in disease affect the gene products. The KD4v (Comprehensible Knowledge Discovery System for Missense Variant) server allows to characterize and predict the phenotypic effects (deleterious/neutral) of missense variants. The server provides a set of rules learned by Induction Logic Programming (ILP) on a set of missense variants described by conservation, physico-chemical, functional and 3D structure predicates. These rules are interpretable by non-expert humans and are used to accurately predict the deleterious/neutral status of an unknown mutation. The web server is available at http://decrypthon.igbmc.fr/kd4v.

Knowledge discovery in variant databases using inductive logic programming.

Understanding the effects of genetic variation on the phenotype of an individual is a major goal of biomedical research, especially for the development of diagnostics and effective therapeutic solutions. In this work, we describe the use of a recent knowledge discovery from database (KDD) approach using inductive logic programming (ILP) to automatically extract knowledge about human monogenic diseases. We extracted background knowledge from MSV3d, a database of all human missense variants mapped to 3D protein structure. In this study, we identified 8,117 mutations in 805 proteins with known three-dimensional structures that were known to be involved in human monogenic disease. Our results help to improve our understanding of the relationships between structural, functional or evolutionary features and deleterious mutations. Our inferred rules can also be applied to predict the impact of any single amino acid replacement on the function of a protein. The interpretable rules are available at http://decrypthon.igbmc.fr/kd4v/.

MSV3d: database of human MisSense Variants mapped to 3D protein structure.

The elucidation of the complex relationships linking genotypic and phenotypic variations to protein structure is a major challenge in the post-genomic era. We present MSV3d (Database of human MisSense Variants mapped to 3D protein structure), a new database that contains detailed annotation of missense variants of all human proteins (20 199 proteins). The multi-level characterization includes details of the physico-chemical changes induced by amino acid modification, as well as information related to the conservation of the mutated residue and its position relative to functional features in the available or predicted 3D model. Major releases of the database are automatically generated and updated regularly in line with the dbSNP (database of Single Nucleotide Polymorphism) and SwissVar releases, by exploiting the extensive Décrypthon computational grid resources. The database (http://decrypthon.igbmc.fr/msv3d) is easily accessible through a simple web interface coupled to a powerful query engine and a standard web service. The content is completely or partially downloadable in XML or flat file formats. Database URL: http://decrypthon.igbmc.fr/msv3d.