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人类5'非翻译区序列的多目标计算优化

Multi-objective computational optimization of human 5' UTR sequences.

作者信息

Yamada Keisuke, Suga Kanta, Abe Naoko, Hashimoto Koji, Tsutsumi Susumu, Inagaki Masahito, Hashiya Fumitaka, Abe Hiroshi, Hamada Michiaki

机构信息

Department of Electrical Engineering and Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan.

Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA 19104, United States.

出版信息

Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf225.

DOI:10.1093/bib/bbaf225
PMID:40413870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12103902/
Abstract

The computational design of messenger RNA (mRNA) sequences is a critical technology for both scientific research and industrial applications. Recent advances in prediction and optimization models have enabled the automatic scoring and optimization of $5^\prime $ UTR sequences, key upstream elements of mRNA. However, fully automated design of $5^\prime $ UTR sequences with more than two objective scores has not yet been explored. In this study, we present a computational pipeline that optimizes human $5^\prime $ UTR sequences in a multi-objective framework, addressing up to four distinct and conflicting objectives. Our work represents an important advancement in the multi-objective computational design of mRNA sequences, paving the way for more sophisticated mRNA engineering.

摘要

信使核糖核酸(mRNA)序列的计算设计是科学研究和工业应用的一项关键技术。预测和优化模型的最新进展已实现对mRNA关键上游元件5′非翻译区(UTR)序列的自动评分和优化。然而,具有两个以上目标分数的5′UTR序列的全自动设计尚未得到探索。在本研究中,我们提出了一种计算流程,该流程在多目标框架下优化人类5′UTR序列,可处理多达四个不同且相互冲突的目标。我们的工作代表了mRNA序列多目标计算设计的一项重要进展,为更复杂的mRNA工程铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/457c59eeddc7/bbaf225f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/e3dffe73d508/bbaf225f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/14d6190d36d5/bbaf225f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/fa4c81bc303d/bbaf225f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/457c59eeddc7/bbaf225f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/e3dffe73d508/bbaf225f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/14d6190d36d5/bbaf225f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/fa4c81bc303d/bbaf225f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed76/12103902/457c59eeddc7/bbaf225f4.jpg

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本文引用的文献

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Optimizing 5'UTRs for mRNA-delivered gene editing using deep learning.利用深度学习优化用于 mRNA 递送的基因编辑的 5'UTR。
Nat Commun. 2024 Jun 20;15(1):5284. doi: 10.1038/s41467-024-49508-2.
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Attenuating ribosome load improves protein output from mRNA by limiting translation-dependent mRNA decay.降低核糖体负荷通过限制翻译依赖性 mRNA 降解来提高 mRNA 的蛋白质输出。
Cell Rep. 2024 Apr 23;43(4):114098. doi: 10.1016/j.celrep.2024.114098. Epub 2024 Apr 15.
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Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures.
带有疏水性光裂解标签的帽类似物能够方便地纯化具有各种帽结构的全长加帽 mRNA。
Nat Commun. 2023 May 11;14(1):2657. doi: 10.1038/s41467-023-38244-8.
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Algorithm for optimized mRNA design improves stability and immunogenicity.优化 mRNA 设计的算法可提高稳定性和免疫原性。
Nature. 2023 Sep;621(7978):396-403. doi: 10.1038/s41586-023-06127-z. Epub 2023 May 2.
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Deep learning models for predicting RNA degradation via dual crowdsourcing.通过双重众包预测RNA降解的深度学习模型
Nat Mach Intell. 2022;4(12):1174-1184. doi: 10.1038/s42256-022-00571-8. Epub 2022 Dec 14.
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Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics.基于 mRNA 的治疗方法中,mRNA 结构、稳定性和翻译的组合优化。
Nat Commun. 2022 Mar 22;13(1):1536. doi: 10.1038/s41467-022-28776-w.
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Machine Learning for Designing Next-Generation mRNA Therapeutics.机器学习在新一代 mRNA 疗法设计中的应用。
Acc Chem Res. 2022 Jan 4;55(1):24-34. doi: 10.1021/acs.accounts.1c00621. Epub 2021 Dec 14.
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Fast activation maximization for molecular sequence design.快速激活最大化的分子序列设计。
BMC Bioinformatics. 2021 Oct 20;22(1):510. doi: 10.1186/s12859-021-04437-5.
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Nucleic Acids Res. 2021 Oct 11;49(18):10604-10617. doi: 10.1093/nar/gkab764.
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