Sep 2026· NAR Genomics and Bioinformatics· Vol 8 3, pp.
lqag103
· 0 citations
Medicine
TL;DR
This work introduces LAMBDA, a benchmark designed to rigorously evaluate genome language model embeddings through phage-bacteria sequence discrimination across four categories of increasing complexity: probing tasks, fine-tuning assessments, diagnostic tests, and genome-wide prophage detection.
Abstract
Transformer-based genomic sequence models represent an emerging frontier in computational biology. Yet, their embeddings have not yet shown the same level of predictive power as natural and protein language models, highlighting a gap between current implementations and theoretical promise. Existing benchmarks for DNA language models primarily focus on classifying regulatory elements in eukaryotic genomes, leaving open the fundamental question of whether these models learn sequence-level features across whole genomes. We introduce LAMBDA, a benchmark designed to rigorously evaluate genome language model embeddings through phage-bacteria sequence discrimination across four categories of increasing complexity: probing tasks, fine-tuning assessments, diagnostic tests, and genome-wide prophage detection. Our comprehensive analysis of current genomic language models provides insight into the importance of training data selection relative to model size, the need for domain-specific training, and the capabilities and limitations of genomic language models for detecting prophage sequences. This benchmark represents a challenging genomic annotation task in the bacterial domain and addresses a key computational problem with direct relevance to microbiology and medicine.
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Phages are introduced as a tractable proving ground for stress-testing GLMs against experimentally grounded genotype-to-phenotype tasks and provide a durable framework for identifying what data and model ingredients are required for biologically reliable prediction.
Emily M. Layton, Michael L. Bernauer, Laura D. Weinstock et al.· bioRxiv· 0 citations
Predicting biological function from genomic sequence remains a major challenge in computational and systems biology. Here, we tested whether the genomic language model Evo2, which encodes context-dependent DNA sequence patterns into embeddings, enables prediction of essential genes in fungi, a phenotype central to fung...
Genolator is presented, a multimodal large language model that integrates embeddings from DNA sequences, amino acid sequences, and protein structures with natural language queries and represents a step towards bridging genomic code and human language through the integration of a multimodal LLM.
M. Danner, Tanhim Islam, M. Begemann et al.· Genome Biology· 0 citations
It is shown that genome-wide enhancer annotations and candidate genetic variants predicted by DNABERT-Enhancer provide valuable resources for genome interpretation in functional and clinical genomics studies and can be explored interactively via the web application.
Rekha Sathian, P. Dutta, Ferhat Ay et al.· Bioinformatics· 0 citations
This work introduces seqme, a modular and highly extendable open-source Python library, containing model-agnostic metrics for evaluating computational methods for biological sequence design, and can be used to evaluate both one-shot generation and iterative optimization.
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