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Paired Refinement Experiments

This directory evaluates masked diffusion as an enhancer refiner rather than as a pure de novo generator.

For each reference sequence x, the script creates edited variants x' under a mutation budget rho, scores both sequences with the trained DeepSTARR predictor, and reports:

delta = predictor(x') - predictor(x)

Experiments covered

  1. Paired delta distribution over rho = 0.01, 0.03, 0.05, 0.10, 0.20.
  2. Mask-selection strategy comparison:
    • random: randomly chosen editable positions.
    • entropy: positions where the diffusion model is most uncertain.
    • logit_gap: positions where the diffusion model most prefers a different base than the current base.
  3. Best-of-N refinement:
    • sample multiple edits per sequence and keep the candidate with the largest predicted activity gain.

Outputs

The default output directory is:

${RESULT_ROOT}/refinement/paired_refinement_test

It contains:

refinement_details.jsonl
refinement_summary.json
paired_delta_by_mask_ratio.png
strategy_delta_violin.png
best_of_n_refinement_curve.png

Recommended command on the GPU server

Run from the repository root. Use explicit environment variables to avoid stale defaults from env.sh.

cd /inspire/hdd/project/intelligentcreativedesign/dangshengqi-253114050252/z-anna/genrl-enhancer-diffusion

PROJECT_ROOT=$(pwd) \
RUN_ROOT=$(pwd)/paper_runs \
DEEPSTARR_DIR=$(pwd)/datas/DeepSTARR-enhancer-activity \
GENERANNO_BASE_MODEL=$(pwd)/models/GENERanno-eukaryote-0.5b-base \
DIFFUSION_MODEL=$(pwd)/saved_model/deepstarr_discrete_diffusion \
PREDICTOR_MODEL=$(pwd)/paper_runs/results/deepstarr_regression/best_model \
REFINEMENT_SPLIT=test \
REFINEMENT_NUM_SEQUENCES=1024 \
REFINEMENT_NUM_SAMPLES=8 \
REFINEMENT_MASK_RATIOS="0.01 0.03 0.05 0.10 0.20" \
REFINEMENT_STRATEGIES="random entropy logit_gap" \
REFINEMENT_DIFFUSION_STEPS=32 \
REFINEMENT_BATCH_SIZE=16 \
PREDICTOR_SCORE_BATCH_SIZE=256 \
TRANSFORMERS_NO_TF=1 \
USE_TF=0 \
TOKENIZERS_PARALLELISM=false \
nohup bash scripts/11_refinement/run_paired_refinement.sh > paired_refinement.log 2>&1 &

For a fast smoke test:

PROJECT_ROOT=$(pwd) \
RUN_ROOT=$(pwd)/paper_runs \
DEEPSTARR_DIR=$(pwd)/datas/DeepSTARR-enhancer-activity \
GENERANNO_BASE_MODEL=$(pwd)/models/GENERanno-eukaryote-0.5b-base \
DIFFUSION_MODEL=$(pwd)/saved_model/deepstarr_discrete_diffusion \
PREDICTOR_MODEL=$(pwd)/paper_runs/results/deepstarr_regression/best_model \
REFINEMENT_SPLIT=valid \
REFINEMENT_NUM_SEQUENCES=64 \
REFINEMENT_NUM_SAMPLES=2 \
REFINEMENT_MASK_RATIOS="0.03 0.10" \
REFINEMENT_STRATEGIES="random logit_gap" \
REFINEMENT_DIFFUSION_STEPS=16 \
REFINEMENT_BATCH_SIZE=16 \
PREDICTOR_SCORE_BATCH_SIZE=128 \
TRANSFORMERS_NO_TF=1 \
USE_TF=0 \
TOKENIZERS_PARALLELISM=false \
nohup bash scripts/11_refinement/run_paired_refinement.sh > paired_refinement_smoke.log 2>&1 &