@inproceedings{long-etal-2026-genomeqa,
title = "{G}enome{QA}: Benchmarking General Large Language Models for Genome Sequence Understanding",
author = "Long, Weicai and
Hou, Yusen and
Feng, Junning and
su, Houcheng and
Yang, Shuo and
Xie, Donglin and
Zhang, Yanlin",
editor = "Liakata, Maria and
Moreira, Viviane P. and
Zhang, Jiajun and
Jurgens, David",
booktitle = "Proceedings of the 64th Annual Meeting of the {A}ssociation for {C}omputational {L}inguistics (Volume 1: Long Papers)",
month = jul,
year = "2026",
address = "San Diego, California, United States",
publisher = "Association for Computational Linguistics",
url = "https://aclanthology.org/2026.acl-long.1655/",
pages = "35771--35792",
ISBN = "979-8-89176-390-6",
abstract = "Large Language Models (LLMs) are increasingly adopted as conversational assistants in genomics, where they are mainly used to reason over biological knowledge, annotations, and analysis outputs through natural language interfaces. However, existing benchmarks either focus on specialized DNA models trained for sequence prediction or evaluate biological knowledge using text-only questions, leaving the behavior of general-purpose LLMs when directly exposed to raw genome sequences underexplored. We introduce GenomeQA, a benchmark designed to provide a controlled evaluation setting for general-purpose LLMs on sequence-based genome inference tasks. GenomeQA comprises 5,200 samples drawn from multiple biological databases, with sequence lengths ranging from 6 to 1,000 base pairs (bp), spanning six task families: Enhancer and Promoter Identification, Splice Site Identification, Taxonomic Classification, Histone Mark Prediction, Transcription Factor Binding Site Prediction, and TF Motif Prediction. Across six frontier LLMs, we find that models often outperform random baselines, particularly on tasks driven by local sequence cues such as GC content and short motifs, while performance degrades on tasks that require more indirect or multi-step inference over sequence patterns. GenomeQA establishes a diagnostic benchmark for studying and improving the use of general-purpose LLMs on raw genomic sequences."
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<abstract>Large Language Models (LLMs) are increasingly adopted as conversational assistants in genomics, where they are mainly used to reason over biological knowledge, annotations, and analysis outputs through natural language interfaces. However, existing benchmarks either focus on specialized DNA models trained for sequence prediction or evaluate biological knowledge using text-only questions, leaving the behavior of general-purpose LLMs when directly exposed to raw genome sequences underexplored. We introduce GenomeQA, a benchmark designed to provide a controlled evaluation setting for general-purpose LLMs on sequence-based genome inference tasks. GenomeQA comprises 5,200 samples drawn from multiple biological databases, with sequence lengths ranging from 6 to 1,000 base pairs (bp), spanning six task families: Enhancer and Promoter Identification, Splice Site Identification, Taxonomic Classification, Histone Mark Prediction, Transcription Factor Binding Site Prediction, and TF Motif Prediction. Across six frontier LLMs, we find that models often outperform random baselines, particularly on tasks driven by local sequence cues such as GC content and short motifs, while performance degrades on tasks that require more indirect or multi-step inference over sequence patterns. GenomeQA establishes a diagnostic benchmark for studying and improving the use of general-purpose LLMs on raw genomic sequences.</abstract>
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%0 Conference Proceedings
%T GenomeQA: Benchmarking General Large Language Models for Genome Sequence Understanding
%A Long, Weicai
%A Hou, Yusen
%A Feng, Junning
%A su, Houcheng
%A Yang, Shuo
%A Xie, Donglin
%A Zhang, Yanlin
%Y Liakata, Maria
%Y Moreira, Viviane P.
%Y Zhang, Jiajun
%Y Jurgens, David
%S Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers)
%D 2026
%8 July
%I Association for Computational Linguistics
%C San Diego, California, United States
%@ 979-8-89176-390-6
%F long-etal-2026-genomeqa
%X Large Language Models (LLMs) are increasingly adopted as conversational assistants in genomics, where they are mainly used to reason over biological knowledge, annotations, and analysis outputs through natural language interfaces. However, existing benchmarks either focus on specialized DNA models trained for sequence prediction or evaluate biological knowledge using text-only questions, leaving the behavior of general-purpose LLMs when directly exposed to raw genome sequences underexplored. We introduce GenomeQA, a benchmark designed to provide a controlled evaluation setting for general-purpose LLMs on sequence-based genome inference tasks. GenomeQA comprises 5,200 samples drawn from multiple biological databases, with sequence lengths ranging from 6 to 1,000 base pairs (bp), spanning six task families: Enhancer and Promoter Identification, Splice Site Identification, Taxonomic Classification, Histone Mark Prediction, Transcription Factor Binding Site Prediction, and TF Motif Prediction. Across six frontier LLMs, we find that models often outperform random baselines, particularly on tasks driven by local sequence cues such as GC content and short motifs, while performance degrades on tasks that require more indirect or multi-step inference over sequence patterns. GenomeQA establishes a diagnostic benchmark for studying and improving the use of general-purpose LLMs on raw genomic sequences.
%U https://aclanthology.org/2026.acl-long.1655/
%P 35771-35792
Markdown (Informal)
[GenomeQA: Benchmarking General Large Language Models for Genome Sequence Understanding](https://aclanthology.org/2026.acl-long.1655/) (Long et al., ACL 2026)
ACL
- Weicai Long, Yusen Hou, Junning Feng, Houcheng su, Shuo Yang, Donglin Xie, and Yanlin Zhang. 2026. GenomeQA: Benchmarking General Large Language Models for Genome Sequence Understanding. In Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers), pages 35771–35792, San Diego, California, United States. Association for Computational Linguistics.