A transformer-encoder-based machine-learning classifier that, instead of analyzing words in sentences, models gene families in genomes, provides a scalable method for identifying engineered sequences without relying on specific marker genes, with potential applications in biosecurity, agriculture, GMO regulation and more.
Abstract
Recent advances in genome editing allow easy genetic manipulation of bacteria, providing them with new traits, some of which could be hazardous, e.g. enhanced virulence or extended resistance to antibiotics. The ability to detect artificially modified bacteria is crucial for identifying potential bio-threats. However, malicious genome editing could be challenging to trace due to the natural exchange of genes among bacteria through horizontal transfer. After curating extensive datasets including natural genomes and simulated edited genomes, we utilized a natural language processing approach to detect edited genomes. We developed a transformer-encoder-based machine-learning classifier that, instead of analyzing words in sentences, models gene families in genomes. After training the model on our datasets, it is able to accurately detect genes artificially added to bacterial genomes due to their unnatural context. Our approach provides a scalable method for identifying engineered sequences without relying on specific marker genes, with potential applications in biosecurity, agriculture, GMO regulation and more.
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.
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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...
One of the central goals of plant functional genomics is to uncover regulatory mechanisms that shape agriculturally important traits to inform crop improvement. Recent advances in machine learning (ML) and artificial intelligence (AI), especially Large Language Models (LLMs), have greatly transformed our ability to der...
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Viruses shape microbial metabolism through auxiliary viral genes (AVGs) that reprogram host metabolism, physiology, and gene regulation during infection. Identifying AVGs is complicated by ambiguous viral versus cellular assignment, inconsistent curation, and reliance on sequence homology that misses divergent function...
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In gene editing, CRISPR-Cas9 has revolutionized the field and led to advancements such as base editing and prime editing. This decade's most significant advancement was the creative convergence of these technologies with artificial intelligence (AI) techniques, particularly deep learning and large language models. The...
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This Mini Review summarizes seq2func modelling in plant regulatory genomics, discusses plant-specific challenges and the complementary value of observational and perturbation assays, and proposes evaluation frameworks based on biologically meaningful distribution shifts.
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