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.

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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
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preprint

CPDD: Adapting an autoregressive DNA language model for bidirectional phage genome modeling

Nannan Wu, Tianyi Qiu, Hao Ding
bioRxiv (Cold Spring Harbor Laboratory)
Machine Learning in Bioinformatics
preprint

CPDD: Adapting an autoregressive DNA language model for bidirectional phage genome modeling

Nannan Wu, Tianyi Qiu, Hao Ding
preprint en

Abstract

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.

bioRxiv (Cold Spring Harbor Laboratory)
Fudan University (CN)
Machine Learning in Bioinformatics
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