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Genomic (DNA) sequences encode an enormous amount of information for gene regulation and protein synthesis. Similar to natural language models, researchers have proposed foundation models in genomics to learn generalizable features from…

There are already many DNA large language models, but most of them still follow traditional uses, such as extracting sequence features for classification tasks. More innovative applications of large language models, such as prompt…

Genomics · Quantitative Biology 2024-10-29 Wang Liang

The modeling of genomic sequences presents unique challenges due to their length and structural complexity. Traditional sequence models struggle to capture long-range dependencies and biological features inherent in DNA. In this work, we…

Computational Engineering, Finance, and Science · Computer Science 2026-03-09 Qirong Yang , Yucheng Guo , Zicheng Liu , Yujie Yang , Qijin Yin , Siyuan Li , Shaomin Ji , Linlin Chao , Xiaoming Zhang , Stan Z. Li

DNA sequences encode critical genetic information, yet their variable length and discrete nature impede direct utilization in deep learning models. Existing DNA representation schemes convert sequences into numerical vectors but fail to…

Genomics · Quantitative Biology 2025-12-16 Zhiyuan Peng , Naifan Zhang , Yuanbo Tang , Yang Li

Genomic language models (gLMs) have shown mostly modest success in identifying evolutionarily constrained elements in mammalian genomes. To address this issue, we introduce a novel framework for training gLMs that explicitly models…

Genomics · Quantitative Biology 2026-03-23 Carlos Albors , Jianan Canal Li , Gonzalo Benegas , Chengzhong Ye , Yun S. Song

This study demonstrates that generative large language models can be utilized in a more flexible manner for DNA sequence analysis and classification tasks compared to traditional transformer encoder-based models. While recent encoder-based…

Computation and Language · Computer Science 2025-03-07 Hyunwoo Yoo

Gene expression is a cellular process that plays a fundamental role in human phenotypical variations and diseases. Despite advances of deep learning models for gene expression prediction, recent benchmarks have revealed their inability to…

Cell Behavior · Quantitative Biology 2024-10-04 Edouardo Honig , Huixin Zhan , Ying Nian Wu , Zijun Frank Zhang

Genomic Foundation Models (GFMs) typically rely on Masked Language Modeling (MLM) or Next-Token Prediction (NTP) to learn the "Laws of Nature". While effective at capturing local syntax, these generative paradigms prioritize token-level…

Large language models (LLMs) have revolutionized natural language processing and are increasingly applied to other sequential data types, including genetic sequences. However, adapting LLMs to genomics presents significant challenges.…

Machine Learning · Computer Science 2025-10-29 Qihao Duan , Bingding Huang , Zhenqiao Song , Irina Lehmann , Lei Gu , Roland Eils , Benjamin Wild

Similar to natural language models, pre-trained genome language models are proposed to capture the underlying intricacies within genomes with unsupervised sequence modeling. They have become essential tools for researchers and practitioners…

Genomics · Quantitative Biology 2024-06-04 Siyuan Li , Zedong Wang , Zicheng Liu , Di Wu , Cheng Tan , Jiangbin Zheng , Yufei Huang , Stan Z. Li

Recent genomic foundation models largely adopt large language model architectures that treat DNA as a one-dimensional token sequence. However, exhaustive sequential reading is structurally misaligned with sparse and discontinuous genomic…

Computer Vision and Pattern Recognition · Computer Science 2026-02-03 Hongxin Xiang , Pengsen Ma , Yunkang Cao , Di Yu , Haowen Chen , Xinyu Yang , Xiangxiang Zeng

Building a general-purpose task model similar to ChatGPT has been an important research direction for gene large language models. Instruction fine-tuning is a key component in building ChatGPT, but existing instructions are primarily based…

Genomics · Quantitative Biology 2024-12-03 Wang Liang

DNA sequence classification requires not only high predictive accuracy but also the ability to uncover latent site interactions, combinatorial regulation, and epistasis-like higher-order dependencies. Although the standard Transformer…

Machine Learning · Computer Science 2026-03-30 Zhixuan Cao , Yishu Xu , Xuang WU

Large Language Models (LLMs) such as Mistral and LLaMA have showcased remarkable performance across various natural language processing (NLP) tasks. Despite their success, these models inherit social biases from the diverse datasets on…

Computation and Language · Computer Science 2024-06-19 Nirmalendu Prakash , Lee Ka Wei Roy

One reason pretraining on self-supervised linguistic tasks is effective is that it teaches models features that are helpful for language understanding. However, we want pretrained models to learn not only to represent linguistic features,…

Computation and Language · Computer Science 2020-10-13 Alex Warstadt , Yian Zhang , Haau-Sing Li , Haokun Liu , Samuel R. Bowman

DNA language models are increasingly used to represent genomic sequence, yet their effectiveness depends critically on how raw nucleotides are converted into model inputs. Unlike natural language, DNA offers no canonical boundaries, making…

Genomics · Quantitative Biology 2026-05-21 Taewon Kim , Jihwan Shin , Hyomin Kim , Youngmok Jung , Jonghoon Lee , Won-Chul Lee , Sungsoo Ahn , Insu Han

Advances in natural language processing and large language models have sparked growing interest in modeling DNA, often referred to as the "language of life". However, DNA modeling poses unique challenges. First, it requires the ability to…

While Large language models (LLMs) have proved able to address some complex reasoning tasks, we also know that they are highly sensitive to input variation, which can lead to different solution paths and final answers. Answer consistency…

Computation and Language · Computer Science 2025-03-05 Huiyuan Lai , Xiao Zhang , Malvina Nissim

Learning useful information across long time lags is a critical and difficult problem for temporal neural models in tasks such as language modeling. Existing architectures that address the issue are often complex and costly to train. The…

Computation and Language · Computer Science 2017-07-18 Alexander G. Ororbia , Tomas Mikolov , David Reitter

Large Language Models (LLMs) demonstrate remarkable generalizability across diverse tasks, yet genomic foundation models (GFMs) still require separate finetuning for each downstream application, creating significant overhead as model sizes…

Genomics · Quantitative Biology 2025-02-07 Zehui Li , Vallijah Subasri , Yifei Shen , Dongsheng Li , Yiren Zhao , Guy-Bart Stan , Caihua Shan
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