CPDD: Adapting an autoregressive DNA language model for bidirectional phage genome modeling
Autoregressive DNA language models generate sequences efficiently from left to right, but many genome-analysis and sequence-editing problems are naturally conditioned on both flanks. We introduce CreatiPhage, a 144.5M-parameter autoregressive DNA language model for bacteriophages, and its diffusion extension, CreatiPhage Diffusion DNA-LM (CPDD). CPDD is a 147.5M-parameter bidirectional discrete diffusion model initialized from the six-epoch CreatiPhage checkpoint. CPDD retains the pretrained Transformer, block attention residuals, and Engram conditional memory, while introducing non-causal attention, a MASK-aware base-5 Engram, centered depthwise convolution, and position-aligned nucleotide readout. Training combines masked and GIDD-style uniformly substituted bases with nucleotide- and amino-acid-level losses over a 10 kb, 32 kb, and whole-source context curriculum. On a screened panel of 522 phage CDSs, CPDD achieves higher random-mask restoration accuracy than a comparable diffusion model and performs well above codon-level references. In a mixed-corruption test, it restores 42.4% of visible incorrect bases. Frozen CPDD representations also support infA fitness prediction and seven-class phage virion protein subtype classification. Controlled evaluations further characterize how restoration depends on visible context and identify opportunities to improve longer-range sequence recovery. Together, these results support scaffold-conditioned sequence modeling as a step towards modular design of phage genomes.
Authors
- Nannan Wu (ORCID: https://orcid.org/0000-0003-1244-0030)
- Tianyi Qiu (ORCID: https://orcid.org/0009-0003-4554-3201)
- Hao Ding (ORCID: https://orcid.org/0009-0001-1866-7183)
Institutions
- Fudan University (CN)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-10
- DOI
- https://doi.org/10.64898/2026.11.07.765118
- Primary Topic
- Machine Learning in Bioinformatics
- Type
- preprint