Yeast Barcoders: a chemogenomic application of a universal donor-strain collection carrying bar-code identifiers

A library of universal Saccharomyces cerevisiae Barcoder strains for efficient tagging is presented. It is used to tag a collection of hypomorphic alleles of essential yeast genes and applied to chemical genetic screens. Also in this issue, Breslow et al. present a similar collection of hypomorphic alleles, coupled with a sensitive growth assay for improved genetic interaction studies. The ability to perform complex bioassays in parallel enables experiments that are otherwise impossible because of throughput and cost constraints. For example, highly parallel chemical-genetic screens using pooled collections of thousands of defined Saccharomyces cerevisiae gene deletion strains are feasible because each strain is bar-coded with unique DNA sequences. It is, however, time-consuming and expensive to individually bar-code individual strains. To provide a simple and general method of barcoding yeast collections, we built a set of donor strains, called Barcoders, with unique bar codes that can be systematically transferred to any S. cerevisiae collection. We applied this technology by generating a collection of bar-coded 'decreased abundance by mRNA perturbation' (DAmP) loss-of-function strains comprising 87.1% of all essential yeast genes. These experiments validate both the Barcoders and the DAmP strain collection as useful tools for genome-wide chemical-genetic assays.