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Related Papers for Controllable Enhancer Generation

This folder collects papers most relevant to the project direction: predictor-guided enhancer design, controllable regulatory DNA generation, and discrete diffusion for biological sequence design.

Downloaded PDFs

File Topic Why it matters for this project
papers/deepstarr_nature_genetics_2022.pdf DeepSTARR enhancer activity predictor and de novo enhancer design Use as the core activity-oracle precedent. The paper validates sequence-to-activity prediction and synthetic enhancer design.
papers/expressiongan_regulatory_dna_natcomm_2022.pdf Generative design of regulatory DNA with ExpressionGAN Useful for sequence-quality analysis: naturalness, expression prediction, edit distance, GC composition, and regulatory grammar.
papers/cell_type_directed_synthetic_enhancers_nature_2024.pdf Cell-type-directed synthetic enhancer design Useful for framing enhancer generation as targeted regulatory design and for activity/specificity evaluation.
papers/coda_cell_type_targeting_cre_nature_2024.pdf Machine-guided CRE design with cell-type targeting Useful for on-target/off-target activity analysis and predictor-guided sequence selection.
papers/dna_diffusion_nature_genetics_2026.pdf DNA-Diffusion for synthetic regulatory elements Closest high-impact diffusion reference: activity, specificity, sequence diversity, and experimental validation.
papers/d3_discrete_diffusion_regulatory_activity_2024.pdf D3 score-entropy discrete diffusion for regulatory DNA Closest methodological reference for conditional discrete diffusion and evaluation with functional, sequence, and motif metrics.
papers/drakes_reward_optimized_discrete_diffusion_2024.pdf Reward optimization for discrete diffusion Useful future-work direction: combine diffusion naturalness with predictor/reward optimization.
papers/atgc_gen_controllable_dna_language_models_2025.pdf Controllable DNA generation with language models Useful baseline framing for autoregressive vs masked-recovery objectives and controllability metrics.
papers/rl_regulatory_dna_design_2025.pdf Reinforcement learning for CRE design Useful baseline/future-work reference for optimizing regulatory DNA with biological priors.

How to Use These Papers in the Manuscript

Recommended related-work grouping:

  1. Sequence-to-activity models for enhancer design: DeepSTARR.
  2. Generative design of regulatory DNA: ExpressionGAN, cell-type-directed synthetic enhancers, CODA.
  3. Controllable genomic language models and reward optimization: ATGC-Gen, RL regulatory DNA design, DRAKES.
  4. Discrete diffusion for regulatory sequence design: D3 and DNA-Diffusion.

Recommended positioning for this project:

This work provides a unified predictor-guided evaluation of autoregressive and masked-diffusion genomic foundation models for controllable enhancer sequence generation on DeepSTARR.

The strongest paper claim should not be "a completely new model" unless more training and benchmarking are added. A safer claim is that the work compares conditioning strategies and evaluation axes for enhancer generation: activity, specificity, diversity, and biological sequence fidelity.