Enhanced interpretation of 935 hotspot and non-hotspot RAS variants using evidence-based structural bioinformatics.

ABSTRACT: In the current study, we report computational scores for advancing genomic interpretation of disease-associated genomic variation in members of the RAS family of genes. For this purpose, we applied 31 sequence- and 3D structure-based computational scores, chosen by their breadth of biophysical properties. We parametrized our data by assembling a numerically homogenized experimentally-derived dataset, which when use in our calculations reveal that computational scores using 3D structure highly correlate with experimental measures (e.g., GAP-mediated hydrolysis R_Spearman = 0.80 and RAF affinity R_spearman = 0.82), while sequence-based scores are discordant with this data. Performing all-against-all comparisons, we applied this parametrized modeling approach to the study

SUBMITTER: Tripathi S 

PROVIDER: S-EPMC8688876 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature