Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity
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, yet the functional roles of the genes identified by these assays often r...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2010
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| Online Access: | http://hdl.handle.net/1721.1/52324 https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-0024-5847 |
| Summary: | 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, yet the functional roles of the genes identified by these assays
often remain enigmatic. By comparing the results of these two assays across various cellular
responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify
response regulators, while 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 harnessed this approach to reveal cellular pathways
related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative
disorders including Parkinson disease. For this we screened an established yeast model for alphasynuclein
toxicity to identify genes that when overexpressed alter cellular survival. Application of
our algorithm to these data and data from mRNA profiling provided functional explanations for many
of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular
pathways. |
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