Towards Increasing the Clinical Relevance of In Silico Methods to Predict Pathogenic Missense Variants
Fig 5
Interpolation plot of predicted endophenotypes resulting from the separate leave-one-out cross-validation calculations shown in Fig 4.
ePOSE score for the 20 CFTR variants from Fig 4 plotted and interpolated (color shows ePOSE scores resulting from training with sweat chloride data). Using the resulting classifiers, each endophenotype was predicted for three additional variants (G551S, A561E, and G1349D) and subsequently validated. A561E was accurately predicted to affect disease via drastically reduced CFTR processing and channel gating. G551S was accurately predicted to affect cystic fibrosis primarily via channel gating.