Journal: Human mutation
Article Title: Objective Assessment of the Evolutionary Action Equation for the Fitness Effect of Missense Mutations Across CAGI Blinded Contests
Figure Lengend Snippet: N-acetyl-glucosaminidase (NAGLU): 165 missense mutants were transfected into HEK293 cells and the NAGLU activity was assessed using a fluorogenic substrate ( A ) The average EA scores for groups of 10 mutants with similar NAGLU activity. Two of the 165 mutants had no experimental assessment and they were omitted. The error bars note the standard error of the mean. ( B ) The average enzymatic activity of NAGLU for groups of 10 mutants with similar EA scores. The error bars note the standard error of the mean. ( C ) The performance of the submitted predictions, according to the overall rank of the CAGI assessor. The assessor used three tests for the overall assessment, the Root-Mean-Square Deviation, the Pearson's Correlation Coefficient, and the Spearman's Rank Correlation Coefficient. The CAGI assessor reported only the best performing method from each research group, since often multiple submissions from the same groups were based on the same original values using different scaling factors. This choice may favor groups with multiple submissions. ( D ) The Pearson's Correlation Coefficients for each submission, calculated by the authors. In addition to the submitted predictions which are shown as colored bars, we calculated Pearson's Correlation Coefficients for PolyPhen2 and SIFT, shown as dashed lines. ( E ) The area under the Receiver Operating Characteristic curve (AUC) for the submitted predictions as function of the threshold of NAGLU activity to separate into deleterious and neutral all 163 mutations or ( F ) the 77 mutations with an experimental standard deviation of σ=0.05 and less. The AUC values were calculated by the authors and they were colored according to the colors of the bars in (D). The dashed lines correspond to predictions from PolyPhen2 and SIFT.
Article Snippet: The enzymatic activity of N-acetyl-glucosaminidase (NAGLU) for 165 missense mutations, which were exclusively found in the ExAC dataset , was assessed as the percentage of the wild-type NAGLU activity by BioMarin Pharmaceutical, Inc.
Techniques: Transfection, Activity Assay, Standard Deviation