m:Explorer: multinomial regression models reveal positive and negative regulators of longevity in yeast quiescence

We developed m:Explorer for identifying process-specific transcription factors (TFs) from multiple genome-wide sources, including transcriptome, DNA-binding and chromatin data. m:Explorer robustly outperforms similar techniques in finding cell cycle TFs in Saccharomyces cerevisiae. We predicted and experimentally tested regulators of quiescence (G(0)), a model of ageing, over a six-week time-course. We validated nine of top-12 predictions as novel G(0 )TFs, including Δmga2, Δcst6, Δbas1 with higher viability and G(0)-essential TFs Tup1, Swi3. Pathway analysis associates longevity to reduced growth, reprogrammed metabolism and cell wall remodeling. m:Explorer (http://biit.cs.ut.ee/mexplorer/) is instrumental in interrogating eukaryotic regulatory systems using heterogeneous data.