Evaluating the genetic diagnostic power of exome sequencing: Identifying missing data.

A hurdle of exome sequencing is its limited capacity to represent the entire exome. To ascertain the diagnostic power of this approach we determined the extent of coverage per individual sample. Using alignment data (BAM files) from 15 exome samples, sequences of any length that were below a determined sequencing depth coverage (DP) were detected and annotated with the Ensembl exon database using MIST, a novel software tool. Samples sequenced at 50X mean coverage had, on average, up to 50% of the Ensembl annotated exons with at least one nucleotide (L=1) with a DP<20, improving to 35% at 100X mean coverage. In addition, almost 15% of annotated exons were never sequenced (L=50, DP<1) at 50x m