mRNA-LM: full-length integrated SLM for mRNA analysis

IF 13.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleic Acids Research Pub Date : 2025-02-03 DOI:10.1093/nar/gkaf044
Sizhen Li, Shahriar Noroozizadeh, Saeed Moayedpour, Lorenzo Kogler-Anele, Zexin Xue, Dinghai Zheng, Fernando Ulloa Montoya, Vikram Agarwal, Ziv Bar-Joseph, Sven Jager
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Abstract

The success of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) messenger RNA (mRNA) vaccine has led to increased interest in the design and use of mRNA for vaccines and therapeutics. Still, selecting the most appropriate mRNA sequence for a protein remains a challenge. Several recent studies have shown that the specific mRNA sequence can have a significant impact on the translation efficiency, half-life, degradation rates, and other issues that play a major role in determining vaccine efficiency. To enable the selection of the most appropriate sequence, we developed mRNA-LM, an integrated small language model for modeling the entire mRNA sequence. mRNA-LM uses the contrastive language–image pretraining integration technology to combine three separate language models for the different mRNA segments. We trained mRNA-LM on millions of diverse mRNA sequences from several different species. The unsupervised model was able to learn meaningful biology related to evolution and host–pathogen interactions. Fine-tuning of mRNA-LM allowed us to use it in several mRNA property prediction tasks. As we show, using the full-length integrated model led to accurate predictions, improving on prior methods proposed for this task.
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mRNA- lm:用于mRNA分析的全长集成SLM
SARS-CoV-2(严重急性呼吸综合征冠状病毒2)信使RNA (mRNA)疫苗的成功,增加了人们对设计和使用mRNA用于疫苗和治疗的兴趣。然而,为蛋白质选择最合适的mRNA序列仍然是一个挑战。最近的几项研究表明,特定的mRNA序列可以对翻译效率、半衰期、降解率和其他在决定疫苗效率方面起主要作用的问题产生重大影响。为了选择最合适的序列,我们开发了mRNA- lm,这是一个集成的小语言模型,用于对整个mRNA序列进行建模。mRNA- lm使用对比语言-图像预训练集成技术,将不同mRNA片段的三个独立语言模型结合在一起。我们对来自不同物种的数百万种不同的mRNA序列进行了mRNA- lm训练。无监督模型能够学习与进化和宿主-病原体相互作用有关的有意义的生物学。对mRNA- lm的微调使我们能够将其用于几个mRNA属性预测任务。正如我们所展示的,使用全长集成模型导致准确的预测,改进了先前为该任务提出的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nucleic Acids Research
Nucleic Acids Research 生物-生化与分子生物学
CiteScore
27.10
自引率
4.70%
发文量
1057
审稿时长
2 months
期刊介绍: Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.
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