Genome modeling and design across all domains of life with Evo 2
Authors:
Top Cited Papers
Preprint
Abstract
All of life encodes information with DNA. While tools for sequencing, synthesis, and editing of genomic code have transformed biological research, intelligently composing new biological systems would also require a deep understanding of the immense complexity encoded by genomes. We introduce Evo 2, a biological foundation model trained on 9.3 trillion DNA base pairs from a highly curated genomic atlas spanning all domains of life. We train Evo 2 with 7B and 40B parameters to have an unprecedented 1 million token context window with single-nucleotide resolution. Evo 2 learns from DNA sequence alone to accurately predict the functional impacts of genetic variation—from noncoding pathogenic mutations to clinically significant BRCA1 variants—without task-specific finetuning. Applying mechanistic interpretability analyses, we reveal that Evo 2 autonomously learns a breadth of biological features, including exon–intron boundaries, transcription factor binding sites, protein structural elements, and prophage genomic regions. Beyond its predictive capabilities, Evo 2 generates mitochondrial, prokaryotic, and eukaryotic sequences at genome scale with greater naturalness and coherence than previous methods. Guiding Evo 2 via inference-time search enables controllable generation of epigenomic structure, for which we demonstrate the first inference-time scaling results in biology. We make Evo 2 fully open, including model parameters, training code, inference code, and the OpenGenome2 dataset, to accelerate the exploration and design of biological complexity.Keywords
This publication has 92 references indexed in Scilit:
- RETRACTED: Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cellsCell, 2024
- SpliceVarDB: A comprehensive database of experimentally validated human splicing variantsThe American Journal of Human Genetics, 2024
- Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sampleCell, 2024
- Convolutions are competitive with transformers for protein sequence pretrainingCell Systems, 2024
- RoFormer: Enhanced transformer with Rotary Position EmbeddingNeurocomputing, 2023
- ProGen2: Exploring the boundaries of protein language modelsCell Systems, 2023
- UCSF ChimeraX : Tools for structure building and analysisProtein Science, 2023
- A Whole-Cell Computational Model Predicts Phenotype from GenotypeCell, 2012
- Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical featuresBiopolymers, 1983
- An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNACell, 1977