DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model
Oligonucleotide aptamers are typically identified through a rigorous and time-consuming process known as systematic evolution of ligands by exponential enrichment (SELEX), which requires 20 to 30 iterative rounds to eliminate non/weak binding sequences and enrich tight binding sequences with high af...
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003238 |
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| author | Xin Yang Chi Ho Chan Shanshan Yao Hang Yin Chu Minchuan Lyu Ziqi Chen Huan Xiao Yuan Ma Sifan Yu Fangfei Li Jin Liu Luyao Wang Zongkang Zhang Bao-Ting Zhang Lu Zhang Aiping Lu Yaofeng Wang Ge Zhang Yuanyuan Yu |
| author_facet | Xin Yang Chi Ho Chan Shanshan Yao Hang Yin Chu Minchuan Lyu Ziqi Chen Huan Xiao Yuan Ma Sifan Yu Fangfei Li Jin Liu Luyao Wang Zongkang Zhang Bao-Ting Zhang Lu Zhang Aiping Lu Yaofeng Wang Ge Zhang Yuanyuan Yu |
| author_sort | Xin Yang |
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| description | Oligonucleotide aptamers are typically identified through a rigorous and time-consuming process known as systematic evolution of ligands by exponential enrichment (SELEX), which requires 20 to 30 iterative rounds to eliminate non/weak binding sequences and enrich tight binding sequences with high affinity. Moreover, inherent experimental biases and non-specific interactions within SELEX could inadvertently exclude high-affinity candidates, leading to a high failure rate. To address these challenges, we proposed DeepAptamer for identifying high-affinity sequences from unenriched early SELEX rounds. As a hybrid neural network model combining convolutional neural networks and bidirectional long short-term memory, DeepAptamer integrated sequence composition and structural features to predict aptamer binding affinities and potential binding motifs. Trained on comprehensive SELEX data, DeepAptamer outperformed existing models in accuracy as substantiated by experimental evidence. More importantly, DeepAptamer effectively identified key nucleotides for target binding. DeepAptamer can efficiently identify high-affinity aptamers against various targets, enhancing its potential to discover promising sequences in initial screening stages and obviating the 20–30 iterative selection rounds required for full enrichment of selection pools. This represented a notable leap forward in aptamer technology, with broad implications for its application across a spectrum of selection targets. |
| format | Article |
| id | doaj-art-7f68fc084d52444d8924efa91893e429 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-7f68fc084d52444d8924efa91893e4292025-01-18T05:04:25ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102436DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning modelXin Yang0Chi Ho Chan1Shanshan Yao2Hang Yin Chu3Minchuan Lyu4Ziqi Chen5Huan Xiao6Yuan Ma7Sifan Yu8Fangfei Li9Jin Liu10Luyao Wang11Zongkang Zhang12Bao-Ting Zhang13Lu Zhang14Aiping Lu15Yaofeng Wang16Ge Zhang17Yuanyuan Yu18Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; Institute of Transdisciplinary Studies, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaGuangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; School of Chinese Medicine, Chinese University of Hong Kong, New Territories, Hong Kong SAR, ChinaGuangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; School of Chinese Medicine, Chinese University of Hong Kong, New Territories, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaGuangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; School of Chinese Medicine, Chinese University of Hong Kong, New Territories, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, ChinaGuangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; School of Chinese Medicine, Chinese University of Hong Kong, New Territories, Hong Kong SAR, ChinaGuangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; School of Chinese Medicine, Chinese University of Hong Kong, New Territories, Hong Kong SAR, ChinaGuangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; Department of Computer Science, Faculty of Science, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; Institute of Systems Medicine and Health Sciences, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Corresponding author: Aiping Lu, Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, New Territories, Hong Kong SAR, China; Corresponding author: Yaofeng Wang, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, New Territories, Hong Kong SAR, China.Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; Institute of Systems Medicine and Health Sciences, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Corresponding author: Ge Zhang, Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Kowloon, Hong Kong SAR, China; Institute of Systems Medicine and Health Sciences, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China; Corresponding author: Yuanyuan Yu, Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.Oligonucleotide aptamers are typically identified through a rigorous and time-consuming process known as systematic evolution of ligands by exponential enrichment (SELEX), which requires 20 to 30 iterative rounds to eliminate non/weak binding sequences and enrich tight binding sequences with high affinity. Moreover, inherent experimental biases and non-specific interactions within SELEX could inadvertently exclude high-affinity candidates, leading to a high failure rate. To address these challenges, we proposed DeepAptamer for identifying high-affinity sequences from unenriched early SELEX rounds. As a hybrid neural network model combining convolutional neural networks and bidirectional long short-term memory, DeepAptamer integrated sequence composition and structural features to predict aptamer binding affinities and potential binding motifs. Trained on comprehensive SELEX data, DeepAptamer outperformed existing models in accuracy as substantiated by experimental evidence. More importantly, DeepAptamer effectively identified key nucleotides for target binding. DeepAptamer can efficiently identify high-affinity aptamers against various targets, enhancing its potential to discover promising sequences in initial screening stages and obviating the 20–30 iterative selection rounds required for full enrichment of selection pools. This represented a notable leap forward in aptamer technology, with broad implications for its application across a spectrum of selection targets.http://www.sciencedirect.com/science/article/pii/S2162253124003238MT: Oligonucleotides: Therapies and ApplicationsaptamersSELEXDNA sequenceDNA shape featureshybrid neural network |
| spellingShingle | Xin Yang Chi Ho Chan Shanshan Yao Hang Yin Chu Minchuan Lyu Ziqi Chen Huan Xiao Yuan Ma Sifan Yu Fangfei Li Jin Liu Luyao Wang Zongkang Zhang Bao-Ting Zhang Lu Zhang Aiping Lu Yaofeng Wang Ge Zhang Yuanyuan Yu DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications aptamers SELEX DNA sequence DNA shape features hybrid neural network |
| title | DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model |
| title_full | DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model |
| title_fullStr | DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model |
| title_full_unstemmed | DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model |
| title_short | DeepAptamer: Advancing high-affinity aptamer discovery with a hybrid deep learning model |
| title_sort | deepaptamer advancing high affinity aptamer discovery with a hybrid deep learning model |
| topic | MT: Oligonucleotides: Therapies and Applications aptamers SELEX DNA sequence DNA shape features hybrid neural network |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003238 |
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