DNA language model GROVER learns sequence context in the human genome

• Published in: Nature machine intelligence Vol. 6; no. 8; pp. 911 - 923
• Main Authors: Sanabria, Melissa, Hirsch, Jonas, Joubert, Pierre M., Poetsch, Anna R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2024; Nature Publishing Group
• Subjects: 631/114/2397; 631/114/2785; 631/208/212; 639/705/1042; 692/308/2056; Accuracy; Annotations; Biological models (mathematics); Context; Data compression; Deep learning; Deoxyribonucleic acid; Dictionaries; DNA; DNA methylation; Engineering; Gene sequencing; Genes; Genomes; Human performance; Language; Large language models; Nucleotides; Representations; Words (language)
• ISSN: 2522-5839; 2522-5839
• DOI: 10.1038/s42256-024-00872-0

Deep-learning models that learn a sense of language on DNA have achieved a high level of performance on genome biological tasks. Genome sequences follow rules similar to natural language but are distinct in the absence of a concept of words. We established byte-pair encoding on the human genome and trained a foundation language model called GROVER (Genome Rules Obtained Via Extracted Representations) with the vocabulary selected via a custom task, next-
k
-mer prediction. The defined dictionary of tokens in the human genome carries best the information content for GROVER. Analysing learned representations, we observed that trained token embeddings primarily encode information related to frequency, sequence content and length. Some tokens are primarily localized in repeats, whereas the majority widely distribute over the genome. GROVER also learns context and lexical ambiguity. Average trained embeddings of genomic regions relate to functional genomics annotation and thus indicate learning of these structures purely from the contextual relationships of tokens. This highlights the extent of information content encoded by the sequence that can be grasped by GROVER. On fine-tuning tasks addressing genome biology with questions of genome element identification and protein–DNA binding, GROVER exceeds other models’ performance. GROVER learns sequence context, a sense for structure and language rules. Extracting this knowledge can be used to compose a grammar book for the code of life.
Genomes can be modelled with language approaches by treating nucleotide bases A, C, G and T like text, but there is no natural concept of what the words would be and whether there is even a ‘language’ to be learned this way. Sanabria et al. have developed a language model called GROVER that learns with a ‘vocabulary’ of genome sequences with byte-pair encoding, a method from text compression, and shows good performance on genome biological tasks.