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

ABSTRACT: 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 ?mga2, ?cst6, ?bas1 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.

SUBMITTER: Reimand J

PROVIDER: S-EPMC3446321 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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

Reimand Jüri J Aun Anu A Vilo Jaak J Vaquerizas Juan M JM Sedman Juhan J Luscombe Nicholas M NM

Genome biology 20120621 6

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 ...[more]

PMID: 22720667

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