Comparative analysis is a powerful means to understand evolution and biology. Sofar we screened 1500 yeast bioactive compounds to identify specific chemical fingerprints for diverse species including S.cerevisiae, S.pombe, C.elegans, E. coli, Danio rerio and Arabidopsis thaliana. In comparison to screens of novel libraries, which yield 2 - 10% bioactivity under the same definitions, a major increase in bioactivity is achieved using pre-screened compounds and accounting for structure activity relationships. Applying a lenient threshold, we found a high degree of bioactivity in these organisms, 40% in S.pombe, 40% in Arabidopsis, 34% in S .cerevisiae, 27 % in zebrafish, 13% in C.elegans and 8% in E. coli. The overlap in compound activity between related species like S.pombe and S.cerevisiae was 22%, whereas the overlap between C.elegans and zebrafish was only 4%. Based on the effects of each compound in the tested organisms, we classified hits as Unique, Selective and Common hits. 98 selective compounds causing reduced growth, interesting phenotypes and structural diversity were profiled using an S.cerevisiae barcoded deletion pool of all homozygous non-essential and heterozygous essential gene-deletion strains to identify compound mechanism of action and putative protein targets. This project is an collaborative effort with people in Liz Patton's, Peter Roy's, Sean Cutler's, Eric Brown's and Guri Giaever's lab. Further details about the project are under restricted access >>
Example showing a specific copper chelator its phenotype in D. rerio and the barcode response of the yeast deletion pool.