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 |
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| author | Yeger-Lotem, Esti Riva, Laura Su, Linhui Julie Gitler, Aaron D. Cashikar, Anil G. King, Oliver D. Auluck, Pavan K. Geddie, Melissa L. Valastyan, Julie Suzanne Lindquist, Susan Fraenkel, Ernest Karger, David R |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Yeger-Lotem, Esti Riva, Laura Su, Linhui Julie Gitler, Aaron D. Cashikar, Anil G. King, Oliver D. Auluck, Pavan K. Geddie, Melissa L. Valastyan, Julie Suzanne Lindquist, Susan Fraenkel, Ernest Karger, David R |
| author_sort | Yeger-Lotem, Esti |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:13:43Z |
| format | Article |
| id | mit-1721.1/52324 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:13:43Z |
| publishDate | 2010 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/523242022-10-02T01:29:17Z Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity Yeger-Lotem, Esti Riva, Laura Su, Linhui Julie Gitler, Aaron D. Cashikar, Anil G. King, Oliver D. Auluck, Pavan K. Geddie, Melissa L. Valastyan, Julie Suzanne Lindquist, Susan Fraenkel, Ernest Karger, David R Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Whitehead Institute for Biomedical Research Karger, David R. Riva, Laura Valastyan, Julie Suzanne Karger, David R. Lindquist, Susan Fraenkel, Ernest 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. MGH/MIT Morris Udall Center of Excellence in PD Research 2010-03-05T13:36:08Z 2010-03-05T13:36:08Z 2009-02 Article http://purl.org/eprint/type/SubmittedJournalArticle 1061-4036 http://hdl.handle.net/1721.1/52324 Yeger-Lotem, Esti et al. “Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity.” Nat Genet 41.3 (2009): 316-323. https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-0024-5847 en_US http://dx.doi.org/10.1038/ng.337 Nature Genetics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group David Karger |
| spellingShingle | Yeger-Lotem, Esti Riva, Laura Su, Linhui Julie Gitler, Aaron D. Cashikar, Anil G. King, Oliver D. Auluck, Pavan K. Geddie, Melissa L. Valastyan, Julie Suzanne Lindquist, Susan Fraenkel, Ernest Karger, David R Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity |
| title | Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity |
| title_full | Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity |
| title_fullStr | Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity |
| title_full_unstemmed | Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity |
| title_short | Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity |
| title_sort | bridging the gap between high throughput genetic and transcriptional data reveals cellular pathways responding to alpha synuclein toxicity |
| url | 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 |
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