Figure 4. Amyloid beta (Aß) nucleation accurately discriminates dominant familial Alzheimer’s disease (fAD) variants.

Receiver operating characteristic (ROC) curves for 12 fAD mutants versus all other single aa mutants in the dataset. Area under the curve (AUC) values are indicated in the legend. Diagonal dashed line indicates the performance of a random classifier. The nucleation scores and categories for all fAD variants are reported in Supplementary file 1.

Figure 4—figure supplement 1. Discrimination of familial Alzheimer’s disease (fAD) variants by aggregation and variant effect predictors.

(A and B) Receiver operating characteristic (ROC) curves built using 12 fAD mutants versus all other single amino acid (aa) mutants in the dataset for variant effect predictors (A) and aggregation predictors (B). Area under the curve (AUC) values are indicated in the legend. Diagonal dashed lines indicate the performance of a random classifier. (C) ROC curve built using 12 fAD mutants versus all other single aa mutants available in the referenced study (Gray et al., 2019). AUC value is indicated in the legend. Diagonal dashed line indicates the performance of a random classifier. (D) Comparison between nucleation scores (NS) and gnomAD (Karczewski, 2020) allele frequencies (https://gnomad.broadinstitute.org/). The horizontal line indicates wild-type (WT) NS (0). The classification of variants is based on Clinvar annotations (https://www.ncbi.nlm.nih.gov/clinvar/). (E) Relation between NS and clinical age-of-onset (Ryman et al., 2014). Vertical and horizontal error lines indicate estimated error associated to NS and standard deviation for age-of-onset, respectively.