Structure-based pathogenicity relationship identifier for predicting effects of single missense variants and discovery of higher-order cancer susceptibility clusters of mutations.

ABSTRACT: We report the structure-based pathogenicity relationship identifier (SPRI), a novel computational tool for accurate evaluation of pathological effects of missense single mutations and prediction of higher-order spatially organized units of mutational clusters. SPRI can effectively extract properties determining pathogenicity encoded in protein structures, and can identify deleterious missense mutations of germ line origin associated with Mendelian diseases, as well as mutations of somatic origin associated with cancer drivers. It compares favorably to other methods in predicting deleterious mutations. Furthermore, SPRI can discover spatially organized pathogenic higher-order spatial clusters (patHOS) of deleterious mutations, including those of low recurrence, and can be used for discovery

SUBMITTER: Wang B 

PROVIDER: S-EPMC10359089 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature