Investigating uncharacterised genes in Saccharomyces cerevisiae using Robot Scientists

YGR067C is an uncharacterised open reading frame in Saccharomyces cerevisiae. We hypothesised that its biological function is to regulate respiration during the diauxic shift. We tested this hypothesis by predicting the effect YGR067C deletion would have on the transcriptomic and metabolomic profiles and then comparing it against empirical data. Predictions of the first-order effects was obtained by curating a list of pathways relevant to the hypothesis and higher-order effects was generated using simulation models based on the GEM Yeast9. Empirical data was generated from biological experiments performed in the Robot Scientist Eve where OD560, transcriptomics, and metabolomics data were generated. We found that YGR067C deletion led to downregulation of transcripts in some ethanol consuming respiratory pathways during the glucose phase. During the ethanol phase, we found that NAD+, NADP+ and NADH had increased accumulation, and several amino acid biosynthesis pathways were enriched for the ygr067c? strain, suggesting longer term consequences of YGR067C mediated regulation. Based on these observations we propose that the role of YGR067C during the diauxic shift is to regulate genes related to ethanol consumption and respiration in the glucose phase. This study demonstrates hypothesis instantiation of previously uncharacterised ORFs combined with automated experimentation protocols for hypothesis verification.