Jun 2026· arXiv.org· Vol abs/2606.30140· 0 citations· 13 references
BiologyComputer Science
TL;DR
This work investigates three key questions: do transformer-based models provide sufficient improvements on fine-tuning tasks upon heavy pretraining, what is the actual contribution of pretraining in this setting, and how does BPE tokenization impact performance on genomics-related tasks.
Abstract
Recent breakthroughs in foundation models and Large Language Models (LLMs) have introduced new opportunities for studying and decoding genomic sequences. Several state-of-the-art approaches, such as DNABERT2, rely on transformer-based architectures, while others, such as ConvNova, still build upon more conventional convolutional models. However, systematic benchmark comparisons across these methods remain scarce. Given that transformer-based models require extensive and costly pretraining, it is crucial to evaluate whether their performance gains justify this overhead. Moreover, LLMs such as DNABERT2 typically rely on Byte Pair Encoding (BPE) tokenization, whose relevance for DNA sequence representation is still debated within the genomics community. In this work, we investigate three key questions: (i) do transformer-based models provide sufficient improvements on fine-tuning tasks upon heavy pretraining, (ii) what is the actual contribution of pretraining in this setting, and (iii) how does BPE tokenization impact performance on genomics-related tasks?
This review provides a comprehensive overview of transformer-based model applications in genomics, transcriptomics, proteomics, drug discovery, drug discovery, and single-cell analysis, and highlights major challenges that remain insufficiently addressed in prior reviews.
Jiajia Liu, Mengyuan Yang, Yankai Yu et al.· Briefings in Bioinformatics· 41 citations· ⚡4
Comparison of GPT-4, BERT (bidirectional encoder representations from transformers), Gemini, and DeepSeek large language models (LLM), focusing on architectures, training methodologies, and real-world applications reveals GPT-4 excels in natural language generation and complex reasoning, supporting up to 128K tokens with moderate latency and higher costs making it effective for conversational artificial intelligence (AI).
Kavish Sanghvi, Aparna S. Sharma, Surbhi Hooda· Computer Science and Informa...· 0 citations
GB.GeneUnet, an 837M-parameter transformer-based U-Net pretrained on 6 trillion tokens from multi-species genomes in OpenGenome2 is introduced, extending genomic context to 1 Mb with up to 100× inference speedup over GeneMoE, a preliminary MoE transformer baseline of similar model size pretrained on the same data.
Ning Sun, William de Vazelhes, Pan Li et al.· bioRxiv· 0 citations
The results suggest that competitive MLLM can emerge from alignment alone, reducing multimodal extension to a lightweight projector-training problem that generalizes across modalities and adapts rapidly to each new LLM release.
Xuanru Zhou, Yiwen Shao, Jiahong Li et al.· 1 citation
Language model tokenizers are typically selected with minimal evaluation, despite the fact that their design choices directly impact model capabilities. This can be partly attributed to a limited understanding of which tokenizer properties affect which aspects of downstream performance. We introduce TokEval, a framework of tokenizer evaluation metrics that goes beyond standard measures like fertility and compression rate to capture linguistically and structurally meaningful properties, e.g., UTF-8 character boundary integrity and digit place-value boundary alignment for mathematics. To validate whether these metrics are predictive of downstream model performance, we conduct controlled language model pretraining experiments, varying solely the tokenizers'training data mixture, pretokenization strategy, and training algorithm. We evaluate the resulting models on bits-per-byte (a tokenizer-agnostic version of perplexity) and several benchmarks, spanning linguistic understanding, mathematical reasoning, and code generation. Our experiments suggest that different intrinsic properties have different impacts on model abilities: information-theoretic metrics predict language modeling abilities (Spearman rho up to 0.80), while structure-sensitive metrics, such as those measuring digit and line-break handling, correlate with task accuracy. We hope TokEval enables more principled tokenizer evaluation, replacing pretraining sweeps with intrinsic measurement wherever the two agree.
A representation-accessibility analysis of frozen genomic language models across regulatory, epigenetic, promoter, splice-site, and variant-effect prediction tasks shows that local biological signal is partially present in frozen representations, but is not always accessible through final pooled embeddings.
Nirjhor Datta, Swakkhar Shatabda, M. S. Rahman· 0 citations