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TrinityDNA: A Bio-Inspired Foundational Model for Efficient Long-Sequence DNA Modeling

Qirong Yang, Yucheng Guo, Zicheng Liu, Yujie Yang, Qijin Yin, Siyuan Li, Shaomin Ji, Linlin Chao, Xiaoming Zhang

2026Year
4Citations
1Top-tier citations

Abstract

The modeling of genomic sequences presents unique challenges due to their long length and structural complexity. Traditional sequence models struggle to capture long-range dependencies and biological features inherent in DNA. In this work, we propose TrinityDNA, a novel DNA foundational model designed to address these challenges. The model integrates biologically informed components, including Groove Fusion for capturing DNA's structural features and Gated Reverse Complement (GRC) to handle the inherent symmetry of DNA sequences. Additionally, we introduce a multi-scale attention mechanism that allows the model to attend to varying levels of sequence dependencies, and an evolutionary training strategy that progressively adapts the model to both prokaryotic and eukaryotic genomes. TrinityDNA provides a more accurate and efficient approach to genomic sequence modeling, offering significant improvements in gene function prediction, regulatory mechanism discovery, and other genomics applications. Our model bridges the gap between machine learning techniques and biological insights, paving the way for more effective analysis of genomic data. Additionally, we introduced a new DNA long-sequence CDS annotation benchmark to make evaluations more comprehensive and oriented toward practical applications.

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