Hyunwoo Yoo

Hyunwoo Yoo

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 models such as DNABERT and Nucleotide Transformer have shown significant performance in DNA sequence classification, transformer decoder-based generative models have not yet been extensively explored in this field. This study evaluates how effectively generative Large Language Models handle DNA sequences with various labels and analyzes performance changes when additional textual information is provided. Experiments were conducted on antimicrobial resistance genes, and the results show that generative Large Language Models can offer comparable or potentially better predictions, demonstrating flexibility and accuracy when incorporating both sequence and textual information. The code and data used in this work are available at the following GitHub repository: https://github.com/biocomgit/llm4dna.

Hyunwoo Yoo, Haebin Shin, Kaidi Xu et al.

DNA Language Models, such as GROVER, DNABERT2 and the Nucleotide Transformer, operate on DNA sequences that inherently contain sequencing errors, mutations, and laboratory-induced noise, which may significantly impact model performance. Despite the importance of this issue, the robustness of DNA language models remains largely underexplored. In this paper, we comprehensivly investigate their robustness in DNA classification by applying various adversarial attack strategies: the character (nucleotide substitutions), word (codon modifications), and sentence levels (back-translation-based transformations) to systematically analyze model vulnerabilities. Our results demonstrate that DNA language models are highly susceptible to adversarial attacks, leading to significant performance degradation. Furthermore, we explore adversarial training method as a defense mechanism, which enhances both robustness and classification accuracy. This study highlights the limitations of DNA language models and underscores the necessity of robustness in bioinformatics.

Hyunwoo Yoo

Since the advent of GANs and VAEs, image generation models have continuously evolved, opening up various real-world applications with the introduction of Stable Diffusion and DALL-E models. These text-to-image models can generate high-quality images for fields such as art, design, and advertising. However, they often produce aberrant images for certain prompts. This study proposes a method to mitigate such issues by fine-tuning the Stable Diffusion 3 model using the DreamBooth technique. Experimental results targeting the prompt "lying on the grass/street" demonstrate that the fine-tuned model shows improved performance in visual evaluation and metrics such as Structural Similarity Index (SSIM), Peak Signal-to-Noise Ratio (PSNR), and Frechet Inception Distance (FID). User surveys also indicated a higher preference for the fine-tuned model. This research is expected to make contributions to enhancing the practicality and reliability of text-to-image models.

Hyunwoo Yoo, Bahrad Sokhansanj, James R. Brown et al.

During times of increasing antibiotic resistance and the spread of infectious diseases like COVID-19, it is important to classify genes related to antibiotic resistance. As natural language processing has advanced with transformer-based language models, many language models that learn characteristics of nucleotide sequences have also emerged. These models show good performance in classifying various features of nucleotide sequences. When classifying nucleotide sequences, not only the sequence itself, but also various background knowledge is utilized. In this study, we use not only a nucleotide sequence-based language model but also a text language model based on PubMed articles to reflect more biological background knowledge in the model. We propose a method to fine-tune the nucleotide sequence language model and the text language model based on various databases of antibiotic resistance genes. We also propose an LLM-based augmentation technique to supplement the data and an ensemble method to effectively combine the two models. We also propose a benchmark for evaluating the model. Our method achieved better performance than the nucleotide sequence language model in the drug resistance class prediction.

Hyunwoo Yoo, Gail Rosen

Microbiome sample representation to input into LLMs is essential for downstream tasks such as phenotype prediction and environmental classification. While prior studies have explored embedding-based representations of each microbiome sample, most rely on simple averaging over sequence embeddings, often overlooking the biological importance of taxa abundance. In this work, we propose an abundance-aware variant of the Set Transformer to construct fixed-size sample-level embeddings by weighting sequence embeddings according to their relative abundance. Without modifying the model architecture, we replicate embedding vectors proportional to their abundance and apply self-attention-based aggregation. Our method outperforms average pooling and unweighted Set Transformers on real-world microbiome classification tasks, achieving perfect performance in some cases. These results demonstrate the utility of abundance-aware aggregation for robust and biologically informed microbiome representation. To the best of our knowledge, this is one of the first approaches to integrate sequence-level abundance into Transformer-based sample embeddings.

Hyunwoo Yoo, Gail L. Rosen

Traditional machine learning models struggle to generalize in microbiome studies where only metadata is available, especially in small-sample settings or across studies with heterogeneous label formats. In this work, we explore the use of large language models (LLMs) to classify microbial samples into ontology categories such as EMPO 3 and related biological labels, as well as to predict pathogen contamination risk, specifically the presence of E. Coli, using environmental metadata alone. We evaluate LLMs such as ChatGPT-4o, Claude 3.7 Sonnet, Grok-3, and LLaMA 4 in zero-shot and few-shot settings, comparing their performance against traditional models like Random Forests across multiple real-world datasets. Our results show that LLMs not only outperform baselines in ontology classification, but also demonstrate strong predictive ability for contamination risk, generalizing across sites and metadata distributions. These findings suggest that LLMs can effectively reason over sparse, heterogeneous biological metadata and offer a promising metadata-only approach for environmental microbiology and biosurveillance applications.