Gene-specific features enhance interpretation of mutational impact on acid α-glucosidase enzyme activity.

ABSTRACT: We present a computational model for predicting mutational impact on enzymatic activity of human acid α-glucosidase (GAA), an enzyme associated with Pompe disease. Using a model that combines features specific to GAA with other general evolutionary and physiochemical features, we made blind predictions of enzymatic activity relative to wildtype human GAA for >300 GAA mutants, as part of the Critical Assessment of Genome Interpretation 5 GAA challenge. We found that gene-specific features can improve the performance of existing impact prediction tools that mostly rely on general features for pathogenicity prediction. Majority of the poorly predicted mutants that lower wildtype GAA enzyme activity occurred on the surface of the GAA protein. We also found that gene-specific features were unco

SUBMITTER: Adhikari AN 

PROVIDER: S-EPMC7329270 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature