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

• Published in: Genome biology 2012-06, Vol.13 (6), p.R55-R55, Article R55
• Main Authors: Reimand, Jüri, Aun, Anu, Vilo, Jaak, Vaquerizas, Juan M, Sedman, Juhan, Luscombe, Nicholas M
• Format: Article
• Language: English
• Subjects: Algorithms; Binding Sites; Cell Cycle; Cell Wall; Cell Wall - genetics; Cell Wall - metabolism; cell walls; Computational Biology; Computational Biology - methods; Gene Expression Regulation, Fungal; Genes, Fungal; genetics; growth & development; Internet; Logistic Models; longevity; Membrane Proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; metabolism; Method; methods; Microbial Viability; Microbial Viability - genetics; Nuclear Proteins; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nucleosomes; Nucleosomes - genetics; Nucleosomes - metabolism; regression analysis; Repressor Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Time Factors; transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; viability; yeasts
• ISSN: 1465-6906; 1474-760X; 1465-6914; 1474-760X
• DOI: 10.1186/gb-2012-13-6-r55

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.