as soon as is submitted to ZB.
Species-aware DNA language models capture regulatory elements and their evolution.
Genome Biol. 25:83 (2024)
BACKGROUND: The rise of large-scale multi-species genome sequencing projects promises to shed new light on how genomes encode gene regulatory instructions. To this end, new algorithms are needed that can leverage conservation to capture regulatory elements while accounting for their evolution. RESULTS: Here, we introduce species-aware DNA language models, which we trained on more than 800 species spanning over 500 million years of evolution. Investigating their ability to predict masked nucleotides from context, we show that DNA language models distinguish transcription factor and RNA-binding protein motifs from background non-coding sequence. Owing to their flexibility, DNA language models capture conserved regulatory elements over much further evolutionary distances than sequence alignment would allow. Remarkably, DNA language models reconstruct motif instances bound in vivo better than unbound ones and account for the evolution of motif sequences and their positional constraints, showing that these models capture functional high-order sequence and evolutionary context. We further show that species-aware training yields improved sequence representations for endogenous and MPRA-based gene expression prediction, as well as motif discovery. CONCLUSIONS: Collectively, these results demonstrate that species-aware DNA language models are a powerful, flexible, and scalable tool to integrate information from large compendia of highly diverged genomes.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Binding; Identification; Divergence; Vertebrate; Sequences; Regions; Protein; Genes; Sites; Rap1
ISSN (print) / ISBN
1474-760X
e-ISSN
1465-6906
Journal
Genome Biology
Quellenangaben
Volume: 25,
Issue: 1,
Article Number: 83
Publisher
BioMed Central
Publishing Place
Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
Bundesministerium fr Bildung und Forschung