Fig. 4

An integrative genomics approach for prioritising noncoding variants. A We performed a rare-variant association study in cardiomyocyte-specific regulatory regions of genes associated with cardiomyopathy. These variants should be tested for deleteriousness or transcriptional activity, and, by inference, for causality. B MPRAs allow for thousands of short DNA sequences to be assayed simultaneously by first synthesising DNA oligos on an array, integrating them into plasmids and inserting into cells. Both input DNA and RNA libraries are sequenced to assess the tag counts associated with the test sequences. Barcode abundance thus scales quantitatively with the regulatory activity of a given tested sequence (figure adapted from Ajore et al. [63]). This technique can be used in future studies to screen all prioritised cardiomyocyte-specific regulatory variants in cardiomyopathy cases