MOTIVATION: During the past 4 years, whole-exome sequencing has become a standard tool for finding rare variants causing Mendelian disorders. In that time, there has also been a proliferation of both sequencing platforms and approaches to analyse their output. This requires approaches to assess the performance of different methods. Traditionally, criteria such as comparison with microarray data or a number of known polymorphic sites have been used. Here we expand such approaches, developing a maximum likelihood framework and using it to estimate the sensitivity and specificity of whole-exome sequencing data. RESULTS: Using whole-exome sequencing data for a panel of 19 individuals, we show that estimated sensitivity and specificity are similar to those calculated using microarray data as a reference. We explore the effect of frequency misspecification arising from using an inappropriately selected population and find that, although the estimates are affected, the rankings across procedures remain the same. AVAILABILITY AND IMPLEMENTATION: An implementation using Perl and R can be found at busso.ncl.ac.uk (Username: igm101; Password: Z1z1nts).

In this paper we describe our initial experiences in the Cloud-e-Genome project with moving the whole exome sequencing pipeline from the scripted HPC-based solution to a workflow enactment system running in the cloud. We discuss shortcomings of the existing approach based on scripts and list benefits that a workflow-based solution can provide. Despite the effort it involved to wrap all required tools in the form of workflow blocks and the restrictions of the dataflow model used to represent workflows we expect the migration to significantly improve the current status of the pipeline. Our target is to enable flexibility, traceability and reproducibility of the solution, so that it can better fit the evolution of tools, data and pipeline itself and allow us to run it at national scale. This work will become foundation for the more complete system that includes variant filtering and interpretation for the diagnostic purposes.