In this week's Nature Genetics, a multi-institute team of researchers reports on a study of the factors that influence the success of whole-genome sequencing for routine clinical diagnosis, finding that while the approach holds promise, there are significant hurdles that must yet be overcome. The investigators sequenced the genomes of 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants, and quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation, and prioritization. While they were able to identify pathogenic variants in some cases, the researchers note that interpreting the results of whole-genome sequencing can often be challenging without additional information and the guidance of those with expertise in particular disorders and in functional validation studies. GenomeWeb has more on this study here.
And in Nature Chemistry, scientists from the University of Cambridge describe a new technique for the rapid and selective regulation of protein function in live mammalian cells. Called bioorthogonal ligand tethering, or BOLT, the method involves the creation of inhibitor-conjugate/protein pairs wherein a target protein contains a genetically encoded unnatural amino acid with bioorthogonal reactivity and the inhibitor conjugate contains a complementary bioorthogonal group. In their study, the group uses the approach to rapidly and specifically inhibit MEK isozymes in live mammalian cells and notes that the introduction of photoisomerizable linkers in the inhibitor conjugate can allow the regulation to be reversed.