m:Explorer: multinomial regression models reveal positive and negative regulators of longevity in yeast quiescence
1 EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
2 University of Tartu, Institute of Computer Science, Liivi 2, Tartu 50409, Estonia
3 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada
4 University of Tartu, Institute of Molecular and Cell Biology, Riia 23, Tartu 51010, Estonia
5 EMBL-Heidelberg Gene Expression Unit, Meyerhofstrasse 1, Heidelberg D-69117, Germany
Genome Biology 2012, 13:R55 doi:10.1186/gb-2012-13-6-r55Published: 21 June 2012
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 (G0), a model of ageing, over a six-week time-course. We validated nine of top-12 predictions as novel G0 TFs, including Δmga2, Δcst6, Δbas1 with higher viability and G0-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.