Predicting Cellular Growth from Gene Expression Signatures (original) (raw)
Figure 6
Predicted growth rates for S. bayanus and S. pombe expression datasets.
By examining genes orthologous to our ∼70 S. cerevisiae growth-specific calibration genes, we successfully applied our model to predict growth rates in S. bayanus (∼50 orthologous growth-specific genes, ∼20 M years diverged) and S. pombe (∼75 growth-specific genes due to one-to-many mappings, ∼1B years diverged). (A) Predicted growth rates for S. bayanus undergoing the diauxic shift from fermentative to respiratory growth (Table S3). As observed for the S. cerevisiae diauxic shift in [4], growth pauses as glucose is exhausted and resumes as the yeast begins consuming ethanol. (B) Predicted growth rates for S. bayanus exposed to a 25–37 C heat shock (Table S3). In contrast to Figure 4B, in which S. cerevisiae is observed to recover from a 37 C heat shock, the less-thermotolerant S. bayanus [28] is predicted to halt growth at high temperatures. (C) Predicted growth rates for S. pombe wild-type and rad3Δ time courses, grown normally and exposed to hydroxyurea (HU, an inhibitor of DNA synthesis and thus growth) [29]. Despite the wide evolutionary divergence between S. pombe and our S. cerevisiae training data, predicted growth rates are in substantial agreement with expected biology. Each time course begins with low growth in a synchronized culture. When the synchronization block is released, cells begin growing, wild-type more efficiently than the rad3Δ mutant. Exposure to HU decreases growth over time, and this effect is exacerbated by RAD3 deletion. While the S. cerevisiae RAD3 ortholog MEC1 is essential, knockouts of the MEC1 pathway members SOD1 and LYS7 have been previously observed to induce HU sensitivity [30].