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Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins

RNA-binding proteins (RBPs) have critical roles in N6-methyladenosine (m6A) modification process. We designed a Random Forest (RF) model to systematically analyze the interaction among RBPs and m6A modifications by integrating the binding signals from hundreds of RBPs. Accurate prediction of m6A sit...

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Detalles Bibliográficos
Autores principales: Hong, Wei, Zhao, Yanding, Weng, Yi-Lan, Cheng, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009289/
https://www.ncbi.nlm.nih.gov/pubmed/36922995
http://dx.doi.org/10.1016/j.isci.2023.106250
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author Hong, Wei
Zhao, Yanding
Weng, Yi-Lan
Cheng, Chao
author_facet Hong, Wei
Zhao, Yanding
Weng, Yi-Lan
Cheng, Chao
author_sort Hong, Wei
collection PubMed
description RNA-binding proteins (RBPs) have critical roles in N6-methyladenosine (m6A) modification process. We designed a Random Forest (RF) model to systematically analyze the interaction among RBPs and m6A modifications by integrating the binding signals from hundreds of RBPs. Accurate prediction of m6A sites demonstrated significant connections between RBP bindings and m6A modifications. The relative importance of different RBPs from the model provided a quantitative metric to evaluate their interactions with m6A modifications. Redundancy analysis showed that several RBPs may have similar binding patterns with m6A sites. The RF model exhibited fairly high prediction accuracy across cell lines, suggesting a conservative RBP interaction network regulates m6A occupancy. Specific RBPs can engage to the corresponding regional m6A sites and deploy distinct regulatory processes, such as cleavage site selection of the alternative polyadenylation (APA). We also integrated histone modifications into our RF model, which demonstrated H3K36me3 and H3K27me3 as determining features for m6A distribution.
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spelling pubmed-100092892023-03-14 Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins Hong, Wei Zhao, Yanding Weng, Yi-Lan Cheng, Chao iScience Article RNA-binding proteins (RBPs) have critical roles in N6-methyladenosine (m6A) modification process. We designed a Random Forest (RF) model to systematically analyze the interaction among RBPs and m6A modifications by integrating the binding signals from hundreds of RBPs. Accurate prediction of m6A sites demonstrated significant connections between RBP bindings and m6A modifications. The relative importance of different RBPs from the model provided a quantitative metric to evaluate their interactions with m6A modifications. Redundancy analysis showed that several RBPs may have similar binding patterns with m6A sites. The RF model exhibited fairly high prediction accuracy across cell lines, suggesting a conservative RBP interaction network regulates m6A occupancy. Specific RBPs can engage to the corresponding regional m6A sites and deploy distinct regulatory processes, such as cleavage site selection of the alternative polyadenylation (APA). We also integrated histone modifications into our RF model, which demonstrated H3K36me3 and H3K27me3 as determining features for m6A distribution. Elsevier 2023-02-20 /pmc/articles/PMC10009289/ /pubmed/36922995 http://dx.doi.org/10.1016/j.isci.2023.106250 Text en © 2023 The Author(s) 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 Article
Hong, Wei
Zhao, Yanding
Weng, Yi-Lan
Cheng, Chao
Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins
title Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins
title_full Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins
title_fullStr Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins
title_full_unstemmed Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins
title_short Random Forest model reveals the interaction between N6-methyladenosine modifications and RNA-binding proteins
title_sort random forest model reveals the interaction between n6-methyladenosine modifications and rna-binding proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009289/
https://www.ncbi.nlm.nih.gov/pubmed/36922995
http://dx.doi.org/10.1016/j.isci.2023.106250
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