UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design

Abstract The 5′ UTR is critical for mRNA stability and translation efficiency in therapeutics. We developed UTR-Insight, a model integrating a pretrained language model with a CNN-Transformer architecture, explaining 89.1% of the mean ribosome load (MRL) variation in random 5′ UTRs and 82.8% in endo...

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Main Authors: Saichao Pan, Hanyu Wang, Hang Zhang, Zan Tang, Lianqiang Xu, Zhixiang Yan, Yong Hu
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-025-11269-7
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author Saichao Pan
Hanyu Wang
Hang Zhang
Zan Tang
Lianqiang Xu
Zhixiang Yan
Yong Hu
author_facet Saichao Pan
Hanyu Wang
Hang Zhang
Zan Tang
Lianqiang Xu
Zhixiang Yan
Yong Hu
author_sort Saichao Pan
collection DOAJ
description Abstract The 5′ UTR is critical for mRNA stability and translation efficiency in therapeutics. We developed UTR-Insight, a model integrating a pretrained language model with a CNN-Transformer architecture, explaining 89.1% of the mean ribosome load (MRL) variation in random 5′ UTRs and 82.8% in endogenous 5′ UTRs, surpassing existing models. Using UTR-Insight, we performed high-throughput in silico screening of hundreds of thousands of endogenous 5′ UTRs from primates, mice, and viruses. The screened sequences increased protein expression by up to 319% compared to the human α-globin 5′ UTR, and UTR-Insight-designed sequences achieved even greater expression levels than high-performing endogenous 5′ UTRs.
format Article
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institution Kabale University
issn 1471-2164
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series BMC Genomics
spelling doaj-art-ea7aafd767f745159aedd87e137bc9842025-02-09T12:13:52ZengBMCBMC Genomics1471-21642025-02-0126111510.1186/s12864-025-11269-7UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and designSaichao Pan0Hanyu Wang1Hang Zhang2Zan Tang3Lianqiang Xu4Zhixiang Yan5Yong Hu6Shenzhen Rhegen Biotechnology Co. LtdShenzhen Rhegen Biotechnology Co. LtdShenzhen Rhegen Biotechnology Co. LtdShenzhen Rhegen Biotechnology Co. LtdShenzhen Rhegen Biotechnology Co. LtdShenzhen Rhegen Biotechnology Co. LtdShenzhen Rhegen Biotechnology Co. LtdAbstract The 5′ UTR is critical for mRNA stability and translation efficiency in therapeutics. We developed UTR-Insight, a model integrating a pretrained language model with a CNN-Transformer architecture, explaining 89.1% of the mean ribosome load (MRL) variation in random 5′ UTRs and 82.8% in endogenous 5′ UTRs, surpassing existing models. Using UTR-Insight, we performed high-throughput in silico screening of hundreds of thousands of endogenous 5′ UTRs from primates, mice, and viruses. The screened sequences increased protein expression by up to 319% compared to the human α-globin 5′ UTR, and UTR-Insight-designed sequences achieved even greater expression levels than high-performing endogenous 5′ UTRs.https://doi.org/10.1186/s12864-025-11269-75′ UTRMean ribosome loadDeep learningmRNA therapeuticsIn silico screening
spellingShingle Saichao Pan
Hanyu Wang
Hang Zhang
Zan Tang
Lianqiang Xu
Zhixiang Yan
Yong Hu
UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design
BMC Genomics
5′ UTR
Mean ribosome load
Deep learning
mRNA therapeutics
In silico screening
title UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design
title_full UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design
title_fullStr UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design
title_full_unstemmed UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design
title_short UTR-Insight: integrating deep learning for efficient 5′ UTR discovery and design
title_sort utr insight integrating deep learning for efficient 5 utr discovery and design
topic 5′ UTR
Mean ribosome load
Deep learning
mRNA therapeutics
In silico screening
url https://doi.org/10.1186/s12864-025-11269-7
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AT hanyuwang utrinsightintegratingdeeplearningforefficient5utrdiscoveryanddesign
AT hangzhang utrinsightintegratingdeeplearningforefficient5utrdiscoveryanddesign
AT zantang utrinsightintegratingdeeplearningforefficient5utrdiscoveryanddesign
AT lianqiangxu utrinsightintegratingdeeplearningforefficient5utrdiscoveryanddesign
AT zhixiangyan utrinsightintegratingdeeplearningforefficient5utrdiscoveryanddesign
AT yonghu utrinsightintegratingdeeplearningforefficient5utrdiscoveryanddesign