Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity

Esti Yeger-Lotem, Laura Riva, Linhui Julie Su, Aaron D. Gitler, Anil G. Cashikar, Oliver D. King, Pavan K. Auluck, Melissa L. Geddie, Julie S. Valastyan, David R. Karger, Susan Lindquist, Ernest Fraenkel

Research output: Contribution to journalArticlepeer-review

233 Scopus citations

Abstract

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens. By comparing the results of these two assays across various stimuli, we found that genetic screens tend to identify response regulators, whereas mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We used this approach to reveal cellular pathways responding to the toxicity of alpha-synuclein, a protein implicated in several neurodegenerative disorders including Parkinson's disease. For this we screened an established yeast model to identify genes that when overexpressed alter alpha-synuclein toxicity. Bridging these data and data from mRNA profiling provided functional explanations for many of these genes and identified previously unknown relations between alpha-synuclein toxicity and basic cellular pathways.

Original languageEnglish
Pages (from-to)316-323
Number of pages8
JournalNature Genetics
Volume41
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Dive into the research topics of 'Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity'. Together they form a unique fingerprint.

Cite this