PhageBench: Can LLMs Understand Raw Bacteriophage Genomes?

Yusen Hou, Weicai Long, Haitao HU, Houcheng su, Junning Feng, Yanlin Zhang


Abstract
Bacteriophages, often referred to as the dark matter of the biosphere, play a critical role in regulating microbial ecosystems and in antibiotic alternatives. Thus, accurate interpretation of their genomes holds significant scientific and practical value. While general-purpose Large Language Models (LLMs) excel at understanding biological texts, their ability to directly interpret raw nucleotide sequences and perform biological reasoning remains underexplored. To address this, we introduce PhageBench, the first benchmark designed to evaluate phage genome understanding by mirroring the workflow of bioinformatics experts. The dataset contains 5,600 high-quality samples covering five core tasks across three stages: Screening, Quality Control, and Phenotype Annotation. Our evaluation of eight LLMs reveals that general-purpose reasoning models significantly outperform random baselines in phage contig identification and host prediction, demonstrating promising potential for genomic understanding. However, they exhibit significant limitations in complex reasoning tasks involving long-range dependencies and fine-grained functional localization. These findings highlight the necessity of developing next-generation models with enhanced reasoning capabilities for biological sequences.
Anthology ID:
2026.findings-acl.1432
Volume:
Findings of the Association for Computational Linguistics: ACL 2026
Month:
July
Year:
2026
Address:
San Diego, California, United States
Editors:
Maria Liakata, Viviane P. Moreira, Jiajun Zhang, David Jurgens
Venue:
Findings
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Publisher:
Association for Computational Linguistics
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Pages:
28674–28698
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URL:
https://preview.aclanthology.org/ingest-acl/2026.findings-acl.1432/
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Cite (ACL):
Yusen Hou, Weicai Long, Haitao HU, Houcheng su, Junning Feng, and Yanlin Zhang. 2026. PhageBench: Can LLMs Understand Raw Bacteriophage Genomes?. In Findings of the Association for Computational Linguistics: ACL 2026, pages 28674–28698, San Diego, California, United States. Association for Computational Linguistics.
Cite (Informal):
PhageBench: Can LLMs Understand Raw Bacteriophage Genomes? (Hou et al., Findings 2026)
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https://preview.aclanthology.org/ingest-acl/2026.findings-acl.1432.pdf
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