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Recent advances in deep learning have relied heavily on the use of large Transformers due to their ability to learn at scale. However, the core building block of Transformers, the attention operator, exhibits quadratic cost in sequence…

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…

Genomic foundation models have the potential to decode DNA syntax, yet face a fundamental tradeoff in their input representation. Standard fixed-vocabulary tokenizers fragment biologically meaningful motifs such as codons and regulatory…

Modeling genomic sequences faces two unsolved challenges: the information density varies widely across different regions, while there is no clearly defined minimum vocabulary unit. Relying on either four primitive bases or independently…

Genomics · Quantitative Biology 2025-11-20 Siyuan Li , Kai Yu , Anna Wang , Zicheng Liu , Chang Yu , Jingbo Zhou , Qirong Yang , Yucheng Guo , Xiaoming Zhang , Stan Z. Li

Processing global geometric context while preserving equivariance is crucial when modeling biological, chemical, and physical systems. Yet, this is challenging due to the computational demands of equivariance and global context at scale.…

Machine Learning · Computer Science 2025-05-29 Artem Moskalev , Mangal Prakash , Junjie Xu , Tianyu Cui , Rui Liao , Tommaso Mansi

Single-cell RNA sequencing (scRNA-seq) has made significant strides in unraveling the intricate cellular diversity within complex tissues. This is particularly critical in the brain, presenting a greater diversity of cell types than other…

Machine Learning · Computer Science 2023-10-05 Gyutaek Oh , Baekgyu Choi , Inkyung Jung , Jong Chul Ye

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

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

The task of understanding and interpreting the complex information encoded within genomic sequences remains a grand challenge in biological research and clinical applications. In this context, recent advancements in large language model…

Genomics · Quantitative Biology 2024-09-25 Qihang Zhao , Chi Zhang , Weixiong Zhang

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,…

Genomics · Quantitative Biology 2026-04-08 Weicai Long , Yusen Hou , Junning Feng , Houcheng Su , Shuo Yang , Donglin Xie , Yanlin Zhang

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

Modeling global geometric context while maintaining equivariance is crucial for accurate predictions in many fields such as biology, chemistry, or vision. Yet, this is challenging due to the computational demands of processing…

Machine Learning · Computer Science 2024-08-14 Artem Moskalev , Mangal Prakash , Rui Liao , Tommaso Mansi

The rapid advancement of DNA sequencing has produced vast genomic datasets, yet interpreting and engineering genomic function remain fundamental challenges. Recent large language models have opened new avenues for genomic analysis, but…

Although DNA foundation models have advanced the understanding of genomes, they still face significant challenges in the limited scale and diversity of genomic data. This limitation starkly contrasts with the success of natural language…

Genomics · Quantitative Biology 2024-02-14 Huixin Zhan , Ying Nian Wu , Zijun Zhang

We introduce Gene42, a novel family of Genomic Foundation Models (GFMs) designed to manage context lengths of up to 192,000 base pairs (bp) at a single-nucleotide resolution. Gene42 models utilize a decoder-only (LLaMA-style) architecture…

DNA sequence alignment involves assigning short DNA reads to the most probable locations on an extensive reference genome. This process is crucial for various genomic analyses, including variant calling, transcriptomics, and epigenomics.…

Foundation models have made significant strides in understanding the genomic language of DNA sequences. However, previous models typically adopt the tokenization methods designed for natural language, which are unsuitable for DNA sequences…

Genomics · Quantitative Biology 2024-12-19 Lifeng Qiao , Peng Ye , Yuchen Ren , Weiqiang Bai , Chaoqi Liang , Xinzhu Ma , Nanqing Dong , Wanli Ouyang

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms. Despite the emergence of numerous deep learning approaches for RNA,…

Quantitative Methods · Quantitative Biology 2024-12-13 Yuchen Ren , Zhiyuan Chen , Lifeng Qiao , Hongtai Jing , Yuchen Cai , Sheng Xu , Peng Ye , Xinzhu Ma , Siqi Sun , Hongliang Yan , Dong Yuan , Wanli Ouyang , Xihui Liu

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

Recent advances in applying deep learning in genomics include DNA-language and single-cell foundation models. However, these models take only one data type as input. We introduce dynamic token adaptation and demonstrate how it combines…

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