A.H MICHEL¹, P. KIMMIG¹, B. KORNMANN<sup>1

1</sup>ETHZ, Institute for Biochemistry/ Otto-Stern-Weg 3, 8093 Zürich

Yeast genetic screens have been absolutely instrumental in our understanding of cell biology. Yet they remain tedious and oftentimes incomplete. Next generation sequencing on the other hand is fast and exhaustive. I have implemented a transposon-based approach combined with deep sequencing to define the complete set of genes that are essential for growth in a particular condition, in one go. The idea is to saturate the yeast genome with independent transposon insertions. Transposons cannot insert in genes that are essential in a given condition. Deep-sequencing of the transposon-genome junctions of the whole library identifies the locations that tolerate the presence of the transposon and allows to deduce those that cannot, revealing the corresponding set of essential genes. The method is readily applicable to multiple growth conditions for comparison. Genes that are essential in one condition and not in another are expected to play a condition-specific physiological role. In addition to identifying essential genes, the method reveals essential protein domains at an unprecedented throughput and resolution.