Sizhen Li, Shahriar Noroozizadeh, Saeed Moayedpour, Lorenzo Kogler-Anele, Zexin Xue, Dinghai Zheng, Fernando Ulloa Montoya, Vikram Agarwal, Ziv Bar-Joseph, Sven Jager
{"title":"mRNA-LM: full-length integrated SLM for mRNA analysis","authors":"Sizhen Li, Shahriar Noroozizadeh, Saeed Moayedpour, Lorenzo Kogler-Anele, Zexin Xue, Dinghai Zheng, Fernando Ulloa Montoya, Vikram Agarwal, Ziv Bar-Joseph, Sven Jager","doi":"10.1093/nar/gkaf044","DOIUrl":null,"url":null,"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.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"4 1","pages":""},"PeriodicalIF":16.6000,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nucleic Acids Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/nar/gkaf044","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.