言語モデルはゲノムを読めるか?より良いワクチンを作るためにmRNAを解読した。(Can language models read the genome? This one decoded mRNA to make better vaccines.)

ad

2024-04-08 プリンストン大学

プリンストン大学の研究者は、遺伝子コードを読み取るための新しい方法を見つけました。これにより、生物学を研究し、医学を改善するために部分的なゲノム配列を最適化することが可能になりました。その成果は、COVID-19などのmRNAワクチンの開発を加速させることに成功しました。この成果は、Nature Machine Intelligence誌に掲載されました

<関連情報>

mRNAの非翻訳領域の解読と機能予測のための5′UTR言語モデル A 5′ UTR language model for decoding untranslated regions of mRNA and function predictions

Yanyi Chu,Dan Yu,Yupeng Li,Kaixuan Huang,Yue Shen,Le Cong,Jason Zhang & Mengdi Wang
Nature Machine Intelligence  Published:05 April 2024
DOI:https://doi.org/10.1038/s42256-024-00823-9

言語モデルはゲノムを読めるか?より良いワクチンを作るためにmRNAを解読した。(Can language models read the genome? This one decoded mRNA to make better vaccines.)

Abstract

The 5′ untranslated region (UTR), a regulatory region at the beginning of a messenger RNA (mRNA) molecule, plays a crucial role in regulating the translation process and affects the protein expression level. Language models have showcased their effectiveness in decoding the functions of protein and genome sequences. Here, we introduce a language model for 5′ UTR, which we refer to as the UTR-LM. The UTR-LM is pretrained on endogenous 5′ UTRs from multiple species and is further augmented with supervised information including secondary structure and minimum free energy. We fine-tuned the UTR-LM in a variety of downstream tasks. The model outperformed the best known benchmark by up to 5% for predicting the mean ribosome loading, and by up to 8% for predicting the translation efficiency and the mRNA expression level. The model was also applied to identifying unannotated internal ribosome entry sites within the untranslated region and improved the area under the precision–recall curve from 0.37 to 0.52 compared to the best baseline. Further, we designed a library of 211 new 5′ UTRs with high predicted values of translation efficiency and evaluated them via a wet-laboratory assay. Experiment results confirmed that our top designs achieved a 32.5% increase in protein production level relative to well-established 5′ UTRs optimized for therapeutics.

細胞遺伝子工学
ad
ad
Follow
ad
タイトルとURLをコピーしました