Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast

Significance The ability to engineer specific behaviors into cells would have a significant impact on biomedicine and biotechnology, including applications to regenerative medicine and biofuels production. One way to coax cells to behave in a desired way is to globally modify their gene expression state, making it more like the state of cells with the desired behavior. This paper introduces a broadly applicable algorithm for transcriptome engineering—designing transcription factor deletions or overexpressions to move cells to a gene expression state that is associated with a desired phenotype. This paper also presents an approach to benchmarking and validating such algorithms. The availability of systematic, objective benchmarks for a computational task often stimulates increased effort and rapid progress on that task.