Deep learning as a bridge between sequencing-derived biological data and functional interpretation

High-throughput sequencing has generated large-scale genomic, transcriptomic, and multimodal datasets, but converting these data into biological interpretation remains difficult because of dimensionality, sparsity, noise, and incomplete ground truth. Deep learning offers flexible representation-learning frameworks for modeling local sequence motifs, long-range dependencies, relational structures, and latent cellular states. In this narrative review, we summarize convolutional, recurrent, graph-based, generative, and transformer architectures and examine representative applications in regulatory genomics, RNA structure prediction, single-cell and spatial transcriptomics, pathology-linked multimodal inference, and proteome-related prediction tasks. We emphasize that these models mainly produce statistical predictions, learned representations, and candidate regulatory signals; they can support functional hypotheses but do not establish biological function without independent validation. We also discuss recurring limitations, including dataset and annotation bias, domain shift, tokenization choices, computational cost, limited reproducibility, incomplete uncertainty quantification, and weak causal identifiability. Finally, we discuss artificial-intelligence virtual cells as an emerging conceptual objective rather than an established capability. Overall, deep learning is framed as a powerful tool for pattern discovery and hypothesis generation, whose biological interpretation requires careful benchmarking, external validation, and experimental follow-up. Advancements in Deep Learning Architectures: This review examines the use of deep learning architectures in bioinformatics, including CNNs, RNNs, GNNs, andTransformers, highlighting their strengths and limitations in modeling complexbiological data. Applications to Genomics: Deep learning has substantially advanced regulatory genomic modeling, RNA structure prediction, single-cell and spatial transcriptomics,pathology-linked multimodal inference, and proteome-related prediction tasks, whilerequiring careful validation before functional interpretation. Challenges and Future Directions: Although deep learning can model individual biological layers (DNA, RNA, proteins), Artificial Intelligence Virtual Cells (AIVCs) remain a conceptual future direction that will require validated multi-omics integration, quantitative calibration, and careful causal testing.

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Publication Details

Journal
Discover Artificial Intelligence
Published
2026-07-26
DOI
https://doi.org/10.1007/s44163-026-01739-6
Primary Topic
Bioinformatics and Genomic Networks
Type
article
Field-Weighted Citation Impact
0.00

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article

Deep learning as a bridge between sequencing-derived biological data and functional interpretation

Shuai Zuo, Shanwen Chen, Jin Zhao, Yongcheng Jin et al.
Discover Artificial Intelligence
Bioinformatics and Genomic Networks
article

Deep learning as a bridge between sequencing-derived biological data and functional interpretation

Shuai Zuo, Shanwen Chen, Jin Zhao, Yongcheng Jin, Wanzhe Liao, Haopeng Hong, Yongzhuo Liu, Runzhu He, Jichang Li, Pengyuan Wang, Lunhui Liu, Xuan He, Lei Sha
article en

Abstract

High-throughput sequencing has generated large-scale genomic, transcriptomic, and multimodal datasets, but converting these data into biological interpretation remains difficult because of dimensionality, sparsity, noise, and incomplete ground truth. Deep learning offers flexible representation-learning frameworks for modeling local sequence motifs, long-range dependencies, relational structures, and latent cellular states. In this narrative review, we summarize convolutional, recurrent, graph-based, generative, and transformer architectures and examine representative applications in regulatory genomics, RNA structure prediction, single-cell and spatial transcriptomics, pathology-linked multimodal inference, and proteome-related prediction tasks. We emphasize that these models mainly produce statistical predictions, learned representations, and candidate regulatory signals; they can support functional hypotheses but do not establish biological function without independent validation. We also discuss recurring limitations, including dataset and annotation bias, domain shift, tokenization choices, computational cost, limited reproducibility, incomplete uncertainty quantification, and weak causal identifiability. Finally, we discuss artificial-intelligence virtual cells as an emerging conceptual objective rather than an established capability. Overall, deep learning is framed as a powerful tool for pattern discovery and hypothesis generation, whose biological interpretation requires careful benchmarking, external validation, and experimental follow-up. Advancements in Deep Learning Architectures: This review examines the use of deep learning architectures in bioinformatics, including CNNs, RNNs, GNNs, andTransformers, highlighting their strengths and limitations in modeling complexbiological data. Applications to Genomics: Deep learning has substantially advanced regulatory genomic modeling, RNA structure prediction, single-cell and spatial transcriptomics,pathology-linked multimodal inference, and proteome-related prediction tasks, whilerequiring careful validation before functional interpretation. Challenges and Future Directions: Although deep learning can model individual biological layers (DNA, RNA, proteins), Artificial Intelligence Virtual Cells (AIVCs) remain a conceptual future direction that will require validated multi-omics integration, quantitative calibration, and careful causal testing.

Discover Artificial Intelligence
Peking University (CN), Guizhou Aerospace Power Science & Tech (China) (CN), Peking University First Hospital (CN), Shenzhen Technology University (CN), Beihang University (CN), Tsinghua University (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 15%
Bioinformatics and Genomic Networks
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