Toward Predictable 5′UTRs in Saccharomyces cerevisiae: Development of a yUTR Calculator
| Autor: | Gert Peters, Sofie De Maeseneire, Marjan De Mey, Thomas Decoene |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Five prime untranslated region Computer science 030106 microbiology Saccharomyces cerevisiae Biomedical Engineering Computational biology Biochemistry Genetics and Molecular Biology (miscellaneous) law.invention 03 medical and health sciences law Computational model biology Sequence Analysis RNA RNA Fungal Regression analysis General Medicine biology.organism_classification 030104 developmental biology Calculator Test set 5' Untranslated Regions Software Pathway engineering Modifying genes |
| Zdroj: | ACS Synthetic Biology. 7:622-634 |
| ISSN: | 2161-5063 |
| DOI: | 10.1021/acssynbio.7b00366 |
| Popis: | Fine-tuning biosynthetic pathways is crucial for the development of economic feasible microbial cell factories. Therefore, the use of computational models able to predictably design regulatory sequences for pathway engineering proves to be a valuable tool, especially for modifying genes at the translational level. In this study we developed a computational approach for the de novo design of 5'-untranslated regions (5'UTRs) in Saccharomyces cerevisiae with a predictive outcome on translation initiation rate. On the basis of existing data, a partial least-squares (PLS) regression model was trained and showed good performance on predicting protein abundances of an independent test set. This model was further used for the construction of a "yUTR calculator" that can design 5'UTR sequences with a diverse range of desired translation efficiencies. The predictive power of our yUTR calculator was confirmed in vivo by different representative case studies. As such, these results show the great potential of data driven approaches for reliable pathway engineering in S. cerevisiae. |
| Databáze: | OpenAIRE |
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