Table 1.
ATP1A3 mutations and clinical features of patients with alternating hemiplegic of childhood.
Table 2.
ATP1A3 mutations identified in 45 Chinese typical AHC patients.
Figure 1.
Locations of ATP1A3 variants and mutations shown on protein domains.
The line represented the protein and the colors of the line represented distance to metal ion binding sites, as the upper left panel showed. The dots represented variants and mutations (for insertion/deletion, the dot marked the beginning position) with the colors representing phenotype categories, as the upper right legend showed. The raw data for this figure was in Table S1.
Figure 2.
Discriminative features and classifier for disease-associated mutations versus neutral variants.
(A) Discriminative effect and correlation of each molecular feature based on training dataset. X-Y axes demonstrated correlation between each feature with variant category through logistic regression analysis and Spearman's rho calculation. The dot color represented the class the molecular feature belonged to, and size meant selected frequency in robust feature selection procedure. The selected features were labeled. (B) Classifiers and its prediction result. X-Y axes represented the selected features ‘cbeta_wt_E2’ (the number of β carbon atoms around the mutated site within 10 Å in E2 wildtype protein structure) and ‘dist_metal_E2’ (the minimum distance from mutated site to metal ion binding pocket in E2 wildtype protein structure; unit Å), belonging to ‘solvent accessibility’ and ‘distance to metal site’ class respectively. The violin diagrams demonstrated the distribution of each feature in each variant category. The crosses indicate singleton mutations in AHC, while dots were mutations used in the train dataset. The size of the dots represented precision weights. The solid line was corresponded to the simplest model without any weight, while the three dotted lines from left to right according to the intercept on X axis were the decision boundaries of three different models (see Methods section): using all mutations for training; weighting train dataset with frequency weight; weighting train dataset with precision weight.
Figure 3.
Mutation frequency comparison of ATP1A3 between Chinese and European/American populations.
(A) Mutation frequency comparison of AHC. Each dot represented one mutation, whose value of X axis was the number of cases carrying this mutation out of 47 Chinese AHC cases, and value of Y axis was the number of carriers out of 106 European/American AHC cases. The background showed the P-value of Fisher's exact test and dashed line represented 0.05 significant level. (B) Overall population difference of ATP1A3 according to Fst values. The dots and solid line represented Fst values of informative SNPs in the populations of Chinese, European and American, and the dotted line represented all eleven populations in HapMap Project. The threshold of Fst were set according to S. Wright [40].