Integrating phenotypic and expression profiles to map arsenic-response networks

Astrid C Haugen,Changchun Deng,Ryan Kelley,Charles J Tucker,Jennifer B Collins,Trey Ideker,Cynthia A Afshari,J Martin Brown,Bennett Van Houten

doi:10.1186/gb-2004-5-12-r95

Abstract

By integrating phenotypic and transcriptional profiling and mapping the data onto metabolic and regulatory networks, it was shown that arsenic probably channels sulfur into glutathione for detoxification, leads to indirect oxidative stress by depleting glutathione pools, and alters protein turnover via arsenation of sulfhydryl groups on proteins.

Highlights

Arsenic is a nonmutagenic carcinogen affecting millions of people
In this study we have catalogued the centers of activity associated with arsenic exposure in yeast, identifying the key neighborhoods of activity in the regulatory and metabolic networks using the visualization tools and algorithms in Cytoscape
The transcriptional profile mapped to the regulatory network, revealing several important nodes (Fhl1, Msn2, Msn4, Yap1, Cad1, Pre1, Hsf1 and Met31) as centers of arsenic-induced activity

Summary

Introduction

Arsenic is a nonmutagenic carcinogen affecting millions of people. The cellular impact of this metalloid in Saccharomyces cerevisiae was determined by profiling global gene expression and sensitivity phenotypes. Global technologies in the budding yeast Saccharomyces cerevisiae have changed the face of biological study from the investigation of individual genes and proteins to a systemsbiology approach involving integration of global gene expression with protein-protein and protein-DNA information [1] These data, when combined with phenotypic profiling of the deletion mutant library of nonessential genes, allow an unparalleled assessment of the responses of yeast to environmental stressors [2,3,4]. Even though a number of arsenic-related genes and processes related to defective DNA repair, increased cell proliferation and oxidative stress have been described, the exact mechanisms of arsenic-related disease remain elusive [11,12,13,14,15,16,17,18,19] This is, in part, due to the lack of an acceptable animal model that faithfully recapitulates human disease [15]

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Conclusion