Fig. 3

Impact of deep sequencing as estimated by aggregate exome sequence data from replicates in least variable individual. a Area-proportional Euler Venn diagram (eulerAPE v3.0) of targeted bases sequenced by standard exome sequencing (regular) and aggregate exome sequencing. Sequenced data are represented within circles of Venn diagram (black numbers), whereas targeted and missed by exome sequencing is represented by the square (red numbers). Left panel represents targeted bases in megabases (Mb), and right panel represents the results as percentage of total targeted bases. b Distribution analysis of number of consecutive targeted bases recovered by deep sequencing to ≥20x. Left panel is a log-log plot of frequency of consecutive targeted bases recovered. Right panel plots the distribution of total number of bases sequenced as a function of consecutive targeted bases recovered by deep sequencing to ≥20x. Red dashed lines represent 95 % confidence interval of loess predicted to the data (blue line). c UCSC genome browser screen shot example of LMNA exon that illustrates the variability of ≥20x sequencing along the length of the exon. The black arrow and red box highlight a known disease causing mutation (c.16C > T; p.Q6X) that is consistently missed at the ≥20x threshold by all three technical replicates, but addressed by aggregate sequencing. Aggregate data covers the entire exon to ≥20x