A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation
A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered pr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105729 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1811095108162945024 |
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| author | Fields, Alexander P. Rodriguez, Edwin H. Jovanovic, Marko Stern-Ginossar, Noam Haas, Brian J. Mertins, Philipp Raychowdhury, Raktima Hacohen, Nir Carr, Steven A. Ingolia, Nicholas T. Regev, Aviv Weissman, Jonathan S. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Fields, Alexander P. Rodriguez, Edwin H. Jovanovic, Marko Stern-Ginossar, Noam Haas, Brian J. Mertins, Philipp Raychowdhury, Raktima Hacohen, Nir Carr, Steven A. Ingolia, Nicholas T. Regev, Aviv Weissman, Jonathan S. |
| author_sort | Fields, Alexander P. |
| collection | MIT |
| description | A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered proteins violate these rules. Here we present an experimental and analytical framework, based on ribosome profiling and linear regression, for systematic identification and quantification of translation. Application of this approach to lipopolysaccharide-stimulated mouse dendritic cells and HCMV-infected human fibroblasts identifies thousands of novel CDSs, including micropeptides and variants of known proteins, that bear the hallmarks of canonical translation and exhibit translation levels and dynamics comparable to that of annotated CDSs. Remarkably, many translation events are identified in both mouse and human cells even when the peptide sequence is not conserved. Our work thus reveals an unexpected complexity to mammalian translation suited to provide both conserved regulatory or protein-based functions. |
| first_indexed | 2024-09-23T16:10:46Z |
| format | Article |
| id | mit-1721.1/105729 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:10:46Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1057292022-09-29T18:46:55Z A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation Fields, Alexander P. Rodriguez, Edwin H. Jovanovic, Marko Stern-Ginossar, Noam Haas, Brian J. Mertins, Philipp Raychowdhury, Raktima Hacohen, Nir Carr, Steven A. Ingolia, Nicholas T. Regev, Aviv Weissman, Jonathan S. Massachusetts Institute of Technology. Department of Biology Regev, Aviv A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered proteins violate these rules. Here we present an experimental and analytical framework, based on ribosome profiling and linear regression, for systematic identification and quantification of translation. Application of this approach to lipopolysaccharide-stimulated mouse dendritic cells and HCMV-infected human fibroblasts identifies thousands of novel CDSs, including micropeptides and variants of known proteins, that bear the hallmarks of canonical translation and exhibit translation levels and dynamics comparable to that of annotated CDSs. Remarkably, many translation events are identified in both mouse and human cells even when the peptide sequence is not conserved. Our work thus reveals an unexpected complexity to mammalian translation suited to provide both conserved regulatory or protein-based functions. Klarman Cell Observatory 2016-12-06T20:00:40Z 2016-12-06T20:00:40Z 2015-12 2015-09 Article http://purl.org/eprint/type/JournalArticle 10972765 1097-4164 http://hdl.handle.net/1721.1/105729 Fields, Alexander P. et al. “A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation.” Molecular Cell 60.5 (2015): 816–827. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1016/j.molcel.2015.11.013 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Fields, Alexander P. Rodriguez, Edwin H. Jovanovic, Marko Stern-Ginossar, Noam Haas, Brian J. Mertins, Philipp Raychowdhury, Raktima Hacohen, Nir Carr, Steven A. Ingolia, Nicholas T. Regev, Aviv Weissman, Jonathan S. A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation |
| title | A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation |
| title_full | A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation |
| title_fullStr | A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation |
| title_full_unstemmed | A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation |
| title_short | A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation |
| title_sort | regression based analysis of ribosome profiling data reveals a conserved complexity to mammalian translation |
| url | http://hdl.handle.net/1721.1/105729 https://orcid.org/0000-0001-8567-2049 |
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