journal article·2026-02-10Open access

Benchmark of Genomic Language Models on Human and Rice Genomic Tasks

Xiaosheng Gao, Shunyao Wu, Weihua Pan

Applied Sciences· Volume 16· Issue 4

Abstract

Genomic Language Models (GLMs), leveraging their vast parameter scales and the similarities between DNA sequences and natural languages, demonstrate immense potential in processing large-scale genomic data and elucidating gene regulation and evolutionary relationships. However, the cross-species generalization capability of large genomic models has not yet been systematically evaluated. This study addresses this critical gap by benchmarking five GLMs (DNABERT-2, GROVER, HyenaDNA, NT-V2, and AgroNT) and a CNN baseline model using human (Homo sapiens) and rice (Oryza sativa) genomes across four downstream tasks: promoter detection, transcription start site (TSS) scanning, species classification, and gene region identification, through both zero-shot testing and fine-tuning. During testing, factors such as hyperparameters, early stopping protocols, and computational resources were fixed to ensure fairness, enabling us to systematically evaluate their performance and cross-species generalization capabilities. The results were further analyzed from multiple mathematical and representational perspectives to provide a more rigorous and objective assessment of each model’s performance. The results show that AgroNT consistently leads on rice tasks, while NT-V2 and DNABERT-2 achieved the best overall performance in fine-tuning and zero-shot experiments, respectively. Although their pretraining data did not include plants, they demonstrate excellent performance on rice-related tasks thanks to cross-species pretraining that enhances their generalization ability across human–rice domains. This benchmark study offers guidance on selecting appropriate genomic language models based on task characteristics and provides insights for future development in this field.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Machine Learning in Bioinformatics · Language and cultural evolution · Genetics, Bioinformatics, and Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

College of Computer Science and Technology, Qingdao University, Qingdao 266071, China

State Key Laboratory of Genome and Multi-Omics Technologies, Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China

Funding

National Key R&D Program of China · National Natural Science Foundation of China · Agricultural Science and Technology Innovation Program · Youth Innovation Program of the Chinese Academy of Agricultural Sciences · Innovation Program of Chinese Academy of Agricultural Sciences · Science and Technology Project of the Ministry of Agriculture and Rural Affairs, P.R.China

References (33)

Show source-provided references
1. Next-generation DNA sequencing10.1038/nbt1486 ↗
2. High-throughput sequencing technologies10.1016/j.molcel.2015.05.004 ↗
3. Genome structure described by formal languages10.1093/nar/12.5.2561 ↗
4. Formal language theory and DNA: An analysis of the generative capacity of specific recombinant behaviors10.1016/S0092-8240(87)90018-8 ↗
5. Ji, S. (1999). The linguistics of DNA: Words, sentences, grammar, phonetics, and semantics. Molecular Strategies in Biological Evolution, New York Academy of Sciences.10.1111/j.1749-6632.1999.tb08916.x ↗
6. King, D., Atlasi, Y., and Rafiee, G. (2025). DNABERT-2: Fine-Tuning a Genomic Language Model for Colorectal Gene Enhancer Classification. arXiv.
7. Li, F., Lu, W., and Bai, Y. (2025). HyenaCircle: A HyenaDNA-based pretrained large language model for long eccDNA prediction. Front. Genet., 16.10.3389/fgene.2025.1641162 ↗
8. Marin, F.I., Teufel, F., Horlacher, M., Madsen, D., Pultz, D., Winther, O., and Boomsma, W. (2024, January 7–11). BEND: Benchmarking DNA Language Models on biologically meaningful tasks. Proceedings of the International Conference on Learning Representations (ICLR), Vienna, Austria.
9. Awasthi, R., Mend Mend Arachchige, G.S., and Zhu, X. (2025). Unsupervised evaluation of pre-trained DNA language model embeddings. BMC Genom., 26.10.1186/s12864-025-11913-2 ↗
10. Benchmarking DNA foundation models for genomic and genetic tasks10.1038/s41467-025-65823-8 ↗
11. Finishing the euchromatic sequence of the human genome10.1038/nature03001 ↗
12. International Rice Genome Sequencing Project, and Sasaki, T. (2005). The map-based sequence of the rice genome. Nature, 436, 793–800.10.1038/nature03895 ↗
13. DNABERT: Pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome10.1093/bioinformatics/btab083 ↗
14. Zhou, Z., Ji, Y., Li, W., Dutta, P., Davuluri, R., and Liu, H. (2023). DNABERT-2: Efficient foundation model and benchmark for multi-species genome. arXiv.
15. DNA language model GROVER learns sequence context in the human genome10.1038/s42256-024-00872-0 ↗
16. Nguyen, E., Poli, M., Faizi, M., Thomas, A., Birch-Sykes, C., Wornow, M., Patel, A., Rabideau, C., Massaroli, S., and Bengio, Y. (2023). HyenaDNA: Long-range genomic sequence modeling at single nucleotide resolution. Advances in Neural Information Processing Systems, MIT Press.
17. Nucleotide Transformer: Building and evaluating robust foundation models for human genomics10.1038/s41592-024-02523-z ↗
18. A foundational large language model for edible plant genomes10.1038/s42003-024-06465-2 ↗
19. Phytozome: A comparative platform for green plant genomics10.1093/nar/gkr944 ↗
20. Ensembl 202510.1093/nar/gkae1071 ↗
21. Scikit-learn: Machine learning in Python
22. Sennrich, R., Haddow, B., and Birch, A. (2016). Neural Machine Translation of Rare Words with Subword Units. Proceedings of the 54th Annual Meeting of the Association for Computational Linguistics, Association for Computational Linguistics.10.18653/v1/P16-1162 ↗
23. Vaswani, A., Shazeer, N., Parmar, N., Uszkoreit, J., Jones, L., Gomez, A.N., Kaiser, Ł., and Polosukhin, I. (2017). Attention is All you Need. Advances in Neural Information Processing Systems, MIT Press.
24. Press, O., Smith, N.A., and Lewis, M. (2021). Train Short, Test Long: Attention with Linear Biases Enables Input Length Extrapolation. arXiv.
25. Dao, T., Fu, D., Ermon, S., Rudra, A., and Ré, C. (2022). FlashAttention: Fast and Memory-Efficient Exact Attention with IO-Awareness. Advances in Neural Information Processing Systems, MIT Press.
26. RoFormer: Enhanced transformer with Rotary Position Embedding10.1016/j.neucom.2023.127063 ↗
27. Poli, M., Massaroli, S., Nguyen, E., Fu, D.Y., Dao, T., Baccus, S., Bengio, Y., Ermon, S., and Ré, C. (2023). Hyena hierarchy: Towards larger convolutional language models. Proceedings of the 40th International Conference on Machine Learning, PMLR.
28. Gu, A., and Dao, T. (2024). Mamba: Linear-Time Sequence Modeling with Selective State Spaces. arXiv.
29. CpG islands and the regulation of transcription10.1101/gad.2037511 ↗
30. Plant Promoters and Terminators for High-Precision Bioengineering10.34133/bdr.0013 ↗
31. Relationship between gene compactness and base composition in rice and human genome10.1080/07391102.2010.10507332 ↗
32. Reig-Valiente, J.L., Marques, L., Talon, M., and Domingo, C. (2018). Genome-wide association study of agronomic traits in rice cultivated in temperate regions. BMC Genom., 19.10.1186/s12864-018-5086-y ↗
33. Decoding plant and animal genome plasticity from differential paleo-evolutionary patterns and processes10.1093/gbe/evs066 ↗