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Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases
E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play key roles in protein degradation. However, a large number of E3 substrate interactions (ESIs) and DUB substrate interactions (DSIs) remain elusive. Here, we present DeepUSI, a deep learning-based framework to identify ESIs and DSIs...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Research Network of Computational and Structural Biotechnology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883182/ https://www.ncbi.nlm.nih.gov/pubmed/36733699 http://dx.doi.org/10.1016/j.csbj.2023.01.021 |
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author | Shu, Yixuan Hai, Yanru Cao, Lihua Wu, Jianmin |
author_facet | Shu, Yixuan Hai, Yanru Cao, Lihua Wu, Jianmin |
author_sort | Shu, Yixuan |
collection | PubMed |
description | E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play key roles in protein degradation. However, a large number of E3 substrate interactions (ESIs) and DUB substrate interactions (DSIs) remain elusive. Here, we present DeepUSI, a deep learning-based framework to identify ESIs and DSIs using the rich information present in protein sequences. Utilizing the collected golden standard dataset, key hyperparameters in the process of model training, including the ones relevant to data sampling and number of epochs, have been systematically assessed. The performance of DeepUSI was thoroughly evaluated by multiple metrics, based on internal and external validation. Application of DeepUSI to cancer-associated E3 and DUB genes identified a list of druggable substrates with functional implications, warranting further investigation. Together, DeepUSI presents a new framework for predicting substrates of E3 ubiquitin ligases and deubiquitinates. |
format | Online Article Text |
id | pubmed-9883182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Research Network of Computational and Structural Biotechnology |
record_format | MEDLINE/PubMed |
spelling | pubmed-98831822023-02-01 Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases Shu, Yixuan Hai, Yanru Cao, Lihua Wu, Jianmin Comput Struct Biotechnol J Research Article E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play key roles in protein degradation. However, a large number of E3 substrate interactions (ESIs) and DUB substrate interactions (DSIs) remain elusive. Here, we present DeepUSI, a deep learning-based framework to identify ESIs and DSIs using the rich information present in protein sequences. Utilizing the collected golden standard dataset, key hyperparameters in the process of model training, including the ones relevant to data sampling and number of epochs, have been systematically assessed. The performance of DeepUSI was thoroughly evaluated by multiple metrics, based on internal and external validation. Application of DeepUSI to cancer-associated E3 and DUB genes identified a list of druggable substrates with functional implications, warranting further investigation. Together, DeepUSI presents a new framework for predicting substrates of E3 ubiquitin ligases and deubiquitinates. Research Network of Computational and Structural Biotechnology 2023-01-18 /pmc/articles/PMC9883182/ /pubmed/36733699 http://dx.doi.org/10.1016/j.csbj.2023.01.021 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Shu, Yixuan Hai, Yanru Cao, Lihua Wu, Jianmin Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases |
title | Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases |
title_full | Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases |
title_fullStr | Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases |
title_full_unstemmed | Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases |
title_short | Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases |
title_sort | deep-learning based approach to identify substrates of human e3 ubiquitin ligases and deubiquitinases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883182/ https://www.ncbi.nlm.nih.gov/pubmed/36733699 http://dx.doi.org/10.1016/j.csbj.2023.01.021 |
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