Fig. 2
Performance readout and visualization of test results for a representative prioritization of exome data by image analysis (PEDIA) case. (a) For each case the exome variants are ordered according to four different scoring approaches, solely by a molecular deleteriousness score (CADD), by a score from image analysis (DeepGestalt), by a combination of a molecular deleteriousness score and a clinical feature–based semantic similarity score (CADD+Phenomizer), or the PEDIA score that includes all three levels of evidence. The sensitivity of the prioritization approach depends on the number of genes that are considered in an ordered list. The top 1 and top 10 accuracy rates correspond to the intersection of the curves at maximum rank 1 and 10. Note that for benchmarking DeepGestalt on the gene level, syndrome similarity scores first have to be mapped to the gene level, resulting in a lower performance compared with the readout on a phenotype level, due to heterogeneity. The area under the curve is largest for PEDIA scoring. (b) The disease-causing gene of the case depicted in Fig. 1 achieves the highest PEDIA score and molecularly confirms the diagnosis of Coffin–Siris syndrome. Other genes associated with similar phenotypes, such as Nicolaides–Baraitser syndrome, also achieved high scores for gestalt but not for variant deleteriousness.
