Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae

Matej Orešič,Paula Jouhten,Eija Rintala,Merja Oja,Merja Penttilä,Erno Lindfors

doi:10.1186/1752-0509-8-16

Matej Orešič, Paula Jouhten + Show 4 more

Open Access

https://doi.org/10.1186/1752-0509-8-16

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Abstract

BackgroundSaccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions. Previously, oxygen-dependent phenotypes have been studied individually at the transcriptional, metabolite, and flux level. However, the regulation of cell phenotype occurs across the different levels of cell function. Integrative analysis of data from multiple levels of cell function in the context of a network of several known biochemical interaction types could enable identification of active regulatory paths not limited to a single level of cell function.ResultsThe graph theoretical method called Enriched Molecular Path detection (EMPath) was extended to enable integrative utilization of transcription and flux data. The utility of the method was demonstrated by detecting paths associated with phenotype differences of S. cerevisiae under three different conditions of oxygen provision: 20.9%, 2.8% and 0.5%. The detection of molecular paths was performed in an integrated genome-scale metabolic and protein-protein interaction network.ConclusionsThe molecular paths associated with the phenotype differences of S. cerevisiae under conditions of different oxygen provisions revealed paths of molecular interactions that could potentially mediate information transfer between processes that respond to the particular oxygen availabilities.

Highlights

Saccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions
A global network of protein kinase and phosphatase interactions that mediate information transfer via post-translational modifications is available for S. cerevisiae [9] along with a large-scale data set on various types of physical protein-protein interactions [10]
There were two comparisons (“2.8% vs. 0.5%, down” and “20.9% vs. 2.8%, down”) in which PPI edges prevailed when a = 0 indicating that in these comparisons metabolic pathways were less coherently transcriptionally down-regulated than the paths following protein-protein interactions

Summary

Introduction

Saccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions. Active paths of regulatory interactions which determine the cell phenotype are concealed in data on cell components belonging to different regulatory levels. Integration of these e.g. a change in a localization or activity of a protein as a result of physical interaction or post-translational modification [5,6,7]. A global network of protein kinase and phosphatase interactions that mediate information transfer via post-translational modifications is available for S. cerevisiae [9] along with a large-scale data set on various types of physical protein-protein interactions [10]

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