pivot: code + trained checkpoints (norman, replogle k562)
#1
by bryan7264 - opened
This view is limited to 50 files because it contains too many changes. See the raw diff here.
- .gitattributes +2 -1
- .gitignore +31 -0
- LICENSE +21 -0
- README.md +90 -3
- experiments/results/gears_norman.json +56 -0
- experiments/results/gears_ranking.json +19 -0
- experiments/results/norman_ablation_components.json +75 -0
- experiments/results/norman_ablation_cost.json +9 -0
- experiments/results/norman_ablation_datascale.json +75 -0
- experiments/results/norman_ablation_guidance_steps.json +41 -0
- experiments/results/norman_ablation_inverse_search.json +41 -0
- experiments/results/norman_ablation_matching.json +75 -0
- experiments/results/norman_ablation_representation.json +75 -0
- experiments/results/norman_ablation_reward.json +35 -0
- experiments/results/norman_benchmark.json +231 -0
- experiments/results/norman_combinatorial.json +271 -0
- experiments/results/norman_distloss.json +27 -0
- experiments/results/norman_extra_ablations.json +44 -0
- experiments/results/norman_forward_cell.json +0 -0
- experiments/results/norman_forward_combination.json +1669 -0
- experiments/results/norman_forward_perturbation.json +2845 -0
- experiments/results/norman_nom_cell.json +2773 -0
- experiments/results/norman_nom_improved.json +295 -0
- experiments/results/norman_nom_perturbation.json +1639 -0
- experiments/results/norman_timing_scaling.json +89 -0
- experiments/results/pivot_vs_gears.json +7 -0
- experiments/results/replogle_k562_forward_cell.json +0 -0
- experiments/results/replogle_k562_forward_gene.json +0 -0
- experiments/results/replogle_k562_forward_perturbation.json +0 -0
- experiments/results/replogle_k562_nom_cell.json +2773 -0
- experiments/results/replogle_k562_nom_improved.json +981 -0
- experiments/results/replogle_k562_nom_perturbation.json +2773 -0
- models/norman/config.json +30 -0
- models/norman/model.ptw +3 -0
- models/norman/train_info.json +427 -0
- models/replogle_k562/config.json +30 -0
- models/replogle_k562/model.ptw +3 -0
- models/replogle_k562/train_info.json +427 -0
- requirements.txt +12 -0
- scripts/extra_ablations.py +110 -0
- scripts/figures.py +172 -0
- scripts/gears_compare.py +58 -0
- scripts/gears_ranking.py +144 -0
- scripts/setup_gears_env.sh +25 -0
- scripts/timing_and_scaling.py +115 -0
- src/__init__.py +0 -0
- src/data/__init__.py +0 -0
- src/data/embeddings.py +86 -0
- src/data/perturb_data.py +223 -0
- src/data/preprocess.py +225 -0
.gitattributes
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*.pb filter=lfs diff=lfs merge=lfs -text
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*.pb filter=lfs diff=lfs merge=lfs -text
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*.pkl filter=lfs diff=lfs merge=lfs -text
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*.pth filter=lfs diff=lfs merge=lfs -text
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*.safetensors filter=lfs diff=lfs merge=lfs -text
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*.zst filter=lfs diff=lfs merge=lfs -text
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models/norman/model.ptw filter=lfs diff=lfs merge=lfs -text
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models/replogle_k562/model.ptw filter=lfs diff=lfs merge=lfs -text
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.gitignore
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# large data & downloads (regenerated from public sources via src/data/preprocess.py)
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/data/
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/gears_data/
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/logs/
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# generated artifacts kept out of the repo
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/paper/
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/figures/
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*.h5ad
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*.npz
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*.npy
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# model checkpoints / large binaries
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*.pt
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*.ckpt
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# python
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__pycache__/
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*.pyc
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*.pyo
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.ipynb_checkpoints/
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# latex build artifacts
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paper/*.aux
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paper/*.bbl
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paper/*.blg
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paper/*.out
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paper/*.log
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# os
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.DS_Store
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LICENSE
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MIT License
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Copyright (c) 2026 Bryan Cheng
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Permission is hereby granted, free of charge, to any person obtaining a copy
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of this software and associated documentation files (the "Software"), to deal
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in the Software without restriction, including without limitation the rights
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to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
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copies of the Software, and to permit persons to whom the Software is
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furnished to do so, subject to the following conditions:
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The above copyright notice and this permission notice shall be included in all
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copies or substantial portions of the Software.
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THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
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IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
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FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
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AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
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LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
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OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
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SOFTWARE.
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README.md
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-
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--
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# PIVOT
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Perturbation-Informed Vector-field Optimization for Transcriptomic state control.
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PIVOT learns a perturbation-conditioned flow map over single-cell state embeddings and
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uses its Jacobian for differentiable inverse design: given a control cell state and a
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desired target state, it nominates gene-level interventions that move cells toward the
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target. The same model also does ordinary forward response prediction.
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## Layout
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```
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src/
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data/ loading + preprocessing of perturb-seq data, splits
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models/ perturbation encoder, flow map, the PIVOT module
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training/ training loop and losses
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evaluation/ inference, rewards, metrics, baselines
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experiments/ drivers for the result tables, ablations, figures
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utils/
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scripts/ figure generation, extra ablations, GEARS comparison
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experiments/ saved result json
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```
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## Setup
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```bash
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pip install -r requirements.txt
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```
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Data is not committed. Download and preprocess from the public sources first (Norman 2019
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and Replogle 2022 are pulled from scPerturb):
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```bash
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python -m src.data.preprocess norman
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python -m src.data.preprocess replogle_k562
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```
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This writes a PCA(50) embedding over 2000 highly variable genes plus the held-out splits to
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`data/processed/<dataset>/`.
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## Running things
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```bash
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# train one model
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python -m src.training.train --dataset norman --split perturbation
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# forward + nomination tables
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python -m src.experiments.run_tables --dataset norman --tables forward_cell forward_perturbation
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# ablations
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python -m src.experiments.run_ablations --dataset norman
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# figures
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python scripts/figures.py
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```
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The GEARS head-to-head runs in its own conda env (older torch + pyg), since the package is
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finicky about versions:
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```bash
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bash scripts/setup_gears_env.sh
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conda run -n pivot_gears python scripts/gears_ranking.py
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```
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## Models
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Trained PIVOT checkpoints live under `models/`:
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- `models/norman/` - trained on Norman 2019 (CRISPRa K562)
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- `models/replogle_k562/` - trained on Replogle 2022 (CRISPRi K562)
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each folder has `model.ptw` (a plain torch state dict), `config.json` (the training config),
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and `train_info.json` (history + run info). loading needs the matching preprocessed dataset,
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since the perturbation encoder vocabulary comes from the data:
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```python
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import json, torch
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from src.data.perturb_data import load_dataset
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from src.training.train import TrainConfig, make_model
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cfg = TrainConfig(**json.load(open("models/norman/config.json")))
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data = load_dataset(cfg.dataset)
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model = make_model(data, cfg, device="cpu")
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model.load_state_dict(torch.load("models/norman/model.ptw", map_location="cpu"))
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model.eval()
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```
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## License
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MIT, Bryan Cheng 2026. See `LICENSE`.
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experiments/results/gears_norman.json
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{
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"n_test_perts": 45,
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"test_perts": [
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"ARID1A+ctrl",
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"ARRDC3+ctrl",
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"ATL1+ctrl",
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"BAK1+ctrl",
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"BCL2L11+BAK1",
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"BCL2L11+TGFBR2",
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"BCL2L11+ctrl",
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"BPGM+ZBTB1",
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"C3orf72+FOXL2",
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"CBFA2T3+ctrl",
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"CBL+TGFBR2",
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"CBL+ctrl",
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"CEBPB+OSR2",
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"CEBPE+PTPN12",
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"CKS1B+ctrl",
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"CNNM4+ctrl",
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"DUSP9+IGDCC3",
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"DUSP9+ctrl",
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"EGR1+ctrl",
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"ETS2+CEBPE",
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"FOXA1+FOXF1",
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"FOXF1+HOXB9",
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"FOXF1+ctrl",
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"GLB1L2+ctrl",
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"HOXC13+ctrl",
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"IGDCC3+PRTG",
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"IRF1+SET",
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"KLF1+CEBPA",
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"KLF1+FOXA1",
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"KMT2A+ctrl",
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"MAP2K3+IKZF3",
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"MAP2K3+MAP2K6",
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"MAPK1+ctrl",
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"NCL+ctrl",
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"PLK4+STIL",
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"PTPN12+UBASH3A",
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"RREB1+ctrl",
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"SNAI1+DLX2",
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"TBX3+TBX2",
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"TGFBR2+ETS2",
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"TGFBR2+ctrl",
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"TSC22D1+ctrl",
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"UBASH3B+PTPN12",
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"ZBTB10+DLX2",
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"ZNF318+ctrl"
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],
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"metrics": {
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"mse": 0.003074304576471655,
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"mse_de": 0.10127744511701167,
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"pearson": 0.9916384220123291,
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"pearson_de": 0.8981071008576287
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}
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}
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experiments/results/gears_ranking.json
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{
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"single": {
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"top1": 0.047619047619047616,
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"top5": 0.19047619047619047,
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"ndcg": 0.14115129481729458,
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"rank": 21.666666666666668,
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"n": 21,
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"med_rank": 19.0
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},
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"combo": {
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"top1": 0.038461538461538464,
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"top5": 0.34615384615384615,
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"overlap": 0.15384615384615385,
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"ndcg": 0.26756681334907767,
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"n": 26
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},
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"n_candidates_single": 101,
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| 18 |
+
"n_candidates_combo": 128
|
| 19 |
+
}
|
experiments/results/norman_ablation_components.json
ADDED
|
@@ -0,0 +1,75 @@
|
|
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|
|
|
|
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|
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|
| 1 |
+
{
|
| 2 |
+
"split": "perturbation",
|
| 3 |
+
"rows": {
|
| 4 |
+
"flow-map-only": {
|
| 5 |
+
"forward": {
|
| 6 |
+
"mse": 0.0017506419577291532,
|
| 7 |
+
"de_corr": 0.8443752184034662,
|
| 8 |
+
"mmd": 0.40636296707676617,
|
| 9 |
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|
| 10 |
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|
| 11 |
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|
| 12 |
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|
| 13 |
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|
| 14 |
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|
| 15 |
+
"endpoint_dist": 0.9921409541910345
|
| 16 |
+
}
|
| 17 |
+
},
|
| 18 |
+
"no-tangent": {
|
| 19 |
+
"forward": {
|
| 20 |
+
"mse": 0.001731510258941079,
|
| 21 |
+
"de_corr": 0.8408393241722691,
|
| 22 |
+
"mmd": 0.37349285466271814,
|
| 23 |
+
"pearson": 0.7714462100349843
|
| 24 |
+
},
|
| 25 |
+
"inverse": {
|
| 26 |
+
"top1": 0.045454545454545456,
|
| 27 |
+
"top5": 0.18181818181818182,
|
| 28 |
+
"ndcg": 0.1446297312285945,
|
| 29 |
+
"endpoint_dist": 0.9842348342592065
|
| 30 |
+
}
|
| 31 |
+
},
|
| 32 |
+
"no-semigroup": {
|
| 33 |
+
"forward": {
|
| 34 |
+
"mse": 0.00195918270780586,
|
| 35 |
+
"de_corr": 0.8041895085826833,
|
| 36 |
+
"mmd": 0.35951861984482014,
|
| 37 |
+
"pearson": 0.721258614925628
|
| 38 |
+
},
|
| 39 |
+
"inverse": {
|
| 40 |
+
"top1": 0.0,
|
| 41 |
+
"top5": 0.09090909090909091,
|
| 42 |
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"ndcg": 0.07627732654967648,
|
| 43 |
+
"endpoint_dist": 1.1208079132166775
|
| 44 |
+
}
|
| 45 |
+
},
|
| 46 |
+
"PIVOT-full": {
|
| 47 |
+
"forward": {
|
| 48 |
+
"mse": 0.0018839154465550042,
|
| 49 |
+
"de_corr": 0.8260913965232829,
|
| 50 |
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"mmd": 0.2779389477818921,
|
| 51 |
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"pearson": 0.7429934785641888
|
| 52 |
+
},
|
| 53 |
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"inverse": {
|
| 54 |
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"top1": 0.0,
|
| 55 |
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"top5": 0.13636363636363635,
|
| 56 |
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"ndcg": 0.0741331706168103,
|
| 57 |
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"endpoint_dist": 1.10553578896956
|
| 58 |
+
}
|
| 59 |
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},
|
| 60 |
+
"EndpointMLP": {
|
| 61 |
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"forward": {
|
| 62 |
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"mse": 0.0011545048934962362,
|
| 63 |
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"de_corr": 0.6582605464661375,
|
| 64 |
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"mmd": 0.048875581526963176,
|
| 65 |
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"pearson": 0.6028436505572593
|
| 66 |
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},
|
| 67 |
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"inverse": {
|
| 68 |
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"top1": 0.13636363636363635,
|
| 69 |
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"top5": 0.22727272727272727,
|
| 70 |
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"ndcg": 0.21410929644360008,
|
| 71 |
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"endpoint_dist": 1.0358923240141436
|
| 72 |
+
}
|
| 73 |
+
}
|
| 74 |
+
}
|
| 75 |
+
}
|
experiments/results/norman_ablation_cost.json
ADDED
|
@@ -0,0 +1,9 @@
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
{
|
| 2 |
+
"split": "perturbation",
|
| 3 |
+
"PIVOT": {
|
| 4 |
+
"params": 892658,
|
| 5 |
+
"train_time_s": 102.39015054702759,
|
| 6 |
+
"rank_time_per_query_s": 0.14307117462158203,
|
| 7 |
+
"candidate_evals": 105
|
| 8 |
+
}
|
| 9 |
+
}
|
experiments/results/norman_ablation_datascale.json
ADDED
|
@@ -0,0 +1,75 @@
|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
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|
|
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|
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|
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|
|
|
|
|
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|
|
|
|
|
| 1 |
+
{
|
| 2 |
+
"split": "perturbation",
|
| 3 |
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"rows": {
|
| 4 |
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"0.1": {
|
| 5 |
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| 6 |
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|
| 7 |
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|
| 8 |
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"mmd": 0.0816293043824765,
|
| 9 |
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|
| 10 |
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|
| 11 |
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|
| 12 |
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| 13 |
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|
| 14 |
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|
| 15 |
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|
| 16 |
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}
|
| 17 |
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},
|
| 18 |
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"0.25": {
|
| 19 |
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"forward": {
|
| 20 |
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"mse": 0.0025015621919165106,
|
| 21 |
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"de_corr": 0.7626386221418989,
|
| 22 |
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|
| 23 |
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"pearson": 0.6617828040046895
|
| 24 |
+
},
|
| 25 |
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"inverse": {
|
| 26 |
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|
| 27 |
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|
| 28 |
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|
| 29 |
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|
| 30 |
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}
|
| 31 |
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},
|
| 32 |
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"0.5": {
|
| 33 |
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"forward": {
|
| 34 |
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"mse": 0.0020840686227026534,
|
| 35 |
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"de_corr": 0.806516168916479,
|
| 36 |
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"mmd": 0.167632126198037,
|
| 37 |
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"pearson": 0.7073832176467205
|
| 38 |
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},
|
| 39 |
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"inverse": {
|
| 40 |
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|
| 41 |
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|
| 42 |
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|
| 43 |
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"endpoint_dist": 1.1461743387308987
|
| 44 |
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}
|
| 45 |
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},
|
| 46 |
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"0.75": {
|
| 47 |
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"forward": {
|
| 48 |
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"mse": 0.002003367400128751,
|
| 49 |
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"de_corr": 0.8197314882616294,
|
| 50 |
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"mmd": 0.23520435415096233,
|
| 51 |
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|
| 52 |
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|
| 53 |
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"inverse": {
|
| 54 |
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|
| 55 |
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|
| 56 |
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|
| 57 |
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"endpoint_dist": 1.1467380632053723
|
| 58 |
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}
|
| 59 |
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},
|
| 60 |
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"1.0": {
|
| 61 |
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"forward": {
|
| 62 |
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"mse": 0.0018839154465550042,
|
| 63 |
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"de_corr": 0.8260913965232829,
|
| 64 |
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"mmd": 0.2779389477818921,
|
| 65 |
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"pearson": 0.7429934785641888
|
| 66 |
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|
| 67 |
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|
| 68 |
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|
| 69 |
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|
| 70 |
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|
| 71 |
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|
| 72 |
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|
| 73 |
+
}
|
| 74 |
+
}
|
| 75 |
+
}
|
experiments/results/norman_ablation_guidance_steps.json
ADDED
|
@@ -0,0 +1,41 @@
|
|
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|
|
|
|
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|
|
|
|
|
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|
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|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
|
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|
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|
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|
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|
|
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|
|
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|
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|
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|
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|
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|
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|
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|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
| 1 |
+
{
|
| 2 |
+
"split": "perturbation",
|
| 3 |
+
"rows": {
|
| 4 |
+
"0": {
|
| 5 |
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|
| 6 |
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|
| 7 |
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|
| 8 |
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"endpoint_dist": 1.10553578896956
|
| 9 |
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},
|
| 10 |
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"5": {
|
| 11 |
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|
| 12 |
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|
| 13 |
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|
| 14 |
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"endpoint_dist": 1.1852125579660588
|
| 15 |
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},
|
| 16 |
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"10": {
|
| 17 |
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"top1": 0.0,
|
| 18 |
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|
| 19 |
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|
| 20 |
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"endpoint_dist": 1.1176448301835493
|
| 21 |
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},
|
| 22 |
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"25": {
|
| 23 |
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|
| 24 |
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|
| 25 |
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|
| 26 |
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"endpoint_dist": 1.2133627290075475
|
| 27 |
+
},
|
| 28 |
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"50": {
|
| 29 |
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|
| 30 |
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|
| 31 |
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|
| 32 |
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"endpoint_dist": 1.146642354401675
|
| 33 |
+
},
|
| 34 |
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"100": {
|
| 35 |
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|
| 36 |
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|
| 37 |
+
"ndcg": 0.0968604433440603,
|
| 38 |
+
"endpoint_dist": 1.168973827903921
|
| 39 |
+
}
|
| 40 |
+
}
|
| 41 |
+
}
|
experiments/results/norman_ablation_inverse_search.json
ADDED
|
@@ -0,0 +1,41 @@
|
|
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|
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|
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|
|
|
|
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|
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|
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|
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|
|
|
|
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|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
|
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|
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|
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|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
{
|
| 2 |
+
"split": "perturbation",
|
| 3 |
+
"rows": {
|
| 4 |
+
"ranking-only": {
|
| 5 |
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"top1": 0.0,
|
| 6 |
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"top5": 0.13636363636363635,
|
| 7 |
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|
| 8 |
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"endpoint_dist": 1.10553578896956
|
| 9 |
+
},
|
| 10 |
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"random-init-opt": {
|
| 11 |
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|
| 12 |
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|
| 13 |
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"ndcg": 0.13006150527926927,
|
| 14 |
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|
| 15 |
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},
|
| 16 |
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"mean-top-init": {
|
| 17 |
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|
| 18 |
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|
| 19 |
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"ndcg": 0.11048529809413464,
|
| 20 |
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"endpoint_dist": 1.633959797295657
|
| 21 |
+
},
|
| 22 |
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"guidance-no-norm": {
|
| 23 |
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"top1": 0.0,
|
| 24 |
+
"top5": 0.18181818181818182,
|
| 25 |
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"ndcg": 0.10475755936295951,
|
| 26 |
+
"endpoint_dist": 2.176489320668307
|
| 27 |
+
},
|
| 28 |
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"guidance-norm": {
|
| 29 |
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"top1": 0.045454545454545456,
|
| 30 |
+
"top5": 0.13636363636363635,
|
| 31 |
+
"ndcg": 0.10540057074853007,
|
| 32 |
+
"endpoint_dist": 1.6980433003468947
|
| 33 |
+
},
|
| 34 |
+
"guidance+rerank": {
|
| 35 |
+
"top1": 0.0,
|
| 36 |
+
"top5": 0.13636363636363635,
|
| 37 |
+
"ndcg": 0.09061663913083162,
|
| 38 |
+
"endpoint_dist": 1.2133627290075475
|
| 39 |
+
}
|
| 40 |
+
}
|
| 41 |
+
}
|
experiments/results/norman_ablation_matching.json
ADDED
|
@@ -0,0 +1,75 @@
|
|
|
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|
|
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|
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|
| 1 |
+
{
|
| 2 |
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"split": "perturbation",
|
| 3 |
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|
| 4 |
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|
| 5 |
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|
| 6 |
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| 7 |
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| 8 |
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| 9 |
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| 10 |
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| 11 |
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| 12 |
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| 13 |
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| 14 |
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| 15 |
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|
| 16 |
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|
| 17 |
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| 18 |
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|
| 19 |
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|
| 20 |
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|
| 21 |
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|
| 22 |
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|
| 23 |
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|
| 24 |
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| 25 |
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| 26 |
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| 27 |
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|
| 28 |
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|
| 29 |
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|
| 30 |
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|
| 31 |
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|
| 32 |
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"celltype": {
|
| 33 |
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"forward": {
|
| 34 |
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"mse": 0.0020935234107186105,
|
| 35 |
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|
| 36 |
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|
| 37 |
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|
| 38 |
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|
| 39 |
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|
| 40 |
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|
| 41 |
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|
| 42 |
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| 43 |
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|
| 44 |
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|
| 45 |
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|
| 46 |
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"batch_celltype": {
|
| 47 |
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|
| 48 |
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"mse": 0.0018839154465550042,
|
| 49 |
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| 50 |
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|
| 51 |
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|
| 52 |
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|
| 53 |
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|
| 54 |
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| 55 |
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| 56 |
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|
| 57 |
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|
| 58 |
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|
| 59 |
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|
| 60 |
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|
| 61 |
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|
| 62 |
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|
| 63 |
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|
| 64 |
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|
| 65 |
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| 66 |
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| 67 |
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| 68 |
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| 69 |
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| 70 |
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| 71 |
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|
| 72 |
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|
| 73 |
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|
| 74 |
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|
| 75 |
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|
experiments/results/norman_ablation_representation.json
ADDED
|
@@ -0,0 +1,75 @@
|
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|
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|
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|
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|
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|
|
|
| 1 |
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{
|
| 2 |
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|
| 3 |
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|
| 4 |
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|
| 5 |
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| 6 |
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|
| 7 |
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| 8 |
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|
| 9 |
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| 10 |
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| 11 |
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| 12 |
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| 13 |
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|
| 14 |
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|
| 15 |
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|
| 16 |
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|
| 17 |
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|
| 18 |
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|
| 19 |
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|
| 20 |
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|
| 21 |
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|
| 22 |
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|
| 23 |
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|
| 24 |
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|
| 25 |
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|
| 26 |
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|
| 27 |
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|
| 28 |
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|
| 29 |
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|
| 30 |
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}
|
| 31 |
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},
|
| 32 |
+
"gene_only": {
|
| 33 |
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"forward": {
|
| 34 |
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"mse": 0.0019814494465963243,
|
| 35 |
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"de_corr": 0.8269104006442618,
|
| 36 |
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"mmd": 0.2864381163653205,
|
| 37 |
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"pearson": 0.7344451238341788
|
| 38 |
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|
| 39 |
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|
| 40 |
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|
| 41 |
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|
| 42 |
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|
| 43 |
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|
| 44 |
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|
| 45 |
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|
| 46 |
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|
| 47 |
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"forward": {
|
| 48 |
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"mse": 0.003925378121029427,
|
| 49 |
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"de_corr": 0.4371013550999317,
|
| 50 |
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|
| 51 |
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|
| 52 |
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|
| 53 |
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|
| 54 |
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|
| 55 |
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|
| 56 |
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|
| 57 |
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|
| 58 |
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}
|
| 59 |
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|
| 60 |
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"gene_pathway_op": {
|
| 61 |
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"forward": {
|
| 62 |
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"mse": 0.002060087917228923,
|
| 63 |
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"de_corr": 0.8255276011818267,
|
| 64 |
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|
| 65 |
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|
| 66 |
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|
| 67 |
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|
| 68 |
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|
| 69 |
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|
| 70 |
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|
| 71 |
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|
| 72 |
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}
|
| 73 |
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}
|
| 74 |
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}
|
| 75 |
+
}
|
experiments/results/norman_ablation_reward.json
ADDED
|
@@ -0,0 +1,35 @@
|
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|
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|
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|
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|
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|
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|
|
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
{
|
| 2 |
+
"split": "perturbation",
|
| 3 |
+
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|
| 4 |
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|
| 5 |
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|
| 6 |
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|
| 7 |
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|
| 8 |
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|
| 9 |
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},
|
| 10 |
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|
| 11 |
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|
| 12 |
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|
| 13 |
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"ndcg": 0.24485694578314335,
|
| 14 |
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"endpoint_dist": 3.251927175305106
|
| 15 |
+
},
|
| 16 |
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"nn_target": {
|
| 17 |
+
"top1": 0.0,
|
| 18 |
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"top5": 0.045454545454545456,
|
| 19 |
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|
| 20 |
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|
| 21 |
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},
|
| 22 |
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|
| 23 |
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|
| 24 |
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|
| 25 |
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|
| 26 |
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|
| 27 |
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|
| 28 |
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"wasserstein": {
|
| 29 |
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|
| 30 |
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|
| 31 |
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|
| 32 |
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"endpoint_dist": 1.222495680505579
|
| 33 |
+
}
|
| 34 |
+
}
|
| 35 |
+
}
|
experiments/results/norman_benchmark.json
ADDED
|
@@ -0,0 +1,231 @@
|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
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|
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|
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|
|
|
|
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|
|
|
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|
|
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|
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|
|
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|
|
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|
|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
|
|
|
|
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|
|
|
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|
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|
|
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|
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|
|
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|
|
|
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|
|
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|
|
|
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|
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|
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|
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|
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|
|
|
|
|
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|
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|
|
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|
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|
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|
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|
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|
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|
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|
|
|
|
|
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|
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|
|
|
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|
|
|
|
|
|
|
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|
|
|
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|
|
|
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|
|
|
|
|
|
|
|
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|
|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
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|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
| 1 |
+
{
|
| 2 |
+
"dataset": "norman",
|
| 3 |
+
"n_targets": 22,
|
| 4 |
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"n_candidates": 105,
|
| 5 |
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"random_top5": 0.047619047619047616,
|
| 6 |
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"forward": {
|
| 7 |
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"PIVOT": {
|
| 8 |
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"mse": 0.0017491921988697326,
|
| 9 |
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"r2": -0.8161821530220357,
|
| 10 |
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"pearson": 0.7693309462133874,
|
| 11 |
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"spearman": 0.5815323970363715,
|
| 12 |
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"de_corr": 0.8388409530545803,
|
| 13 |
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"mmd": 0.3034484875795543,
|
| 14 |
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"wasserstein": 0.43272001688923617
|
| 15 |
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},
|
| 16 |
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"PIVOT-OT": {
|
| 17 |
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"mse": 0.0025015840371278054,
|
| 18 |
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"r2": -2.4559457745957882,
|
| 19 |
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"pearson": 0.6559229388516,
|
| 20 |
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"spearman": 0.46955744461871557,
|
| 21 |
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"de_corr": 0.7519170356557724,
|
| 22 |
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"mmd": 0.1500954119146127,
|
| 23 |
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"wasserstein": 0.6666752559372957
|
| 24 |
+
},
|
| 25 |
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"MeanControl": {
|
| 26 |
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"mse": 0.004455934176339144,
|
| 27 |
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"r2": -0.05741366300177067,
|
| 28 |
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"pearson": 0.06247465056862603,
|
| 29 |
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"spearman": 0.019984302966237155,
|
| 30 |
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"de_corr": 0.10322069715797663,
|
| 31 |
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"mmd": 0.10706937820897701,
|
| 32 |
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|
experiments/results/norman_combinatorial.json
ADDED
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@@ -0,0 +1,271 @@
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experiments/results/norman_distloss.json
ADDED
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@@ -0,0 +1,27 @@
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{
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|
experiments/results/norman_extra_ablations.json
ADDED
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@@ -0,0 +1,44 @@
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|
| 33 |
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| 34 |
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| 44 |
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|
experiments/results/norman_forward_cell.json
ADDED
|
The diff for this file is too large to render.
See raw diff
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|
|
experiments/results/norman_forward_combination.json
ADDED
|
@@ -0,0 +1,1669 @@
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|
| 1 |
+
{
|
| 2 |
+
"split": "combination",
|
| 3 |
+
"models": {
|
| 4 |
+
"PIVOT": {
|
| 5 |
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"mse": 0.0011608018271195202,
|
| 6 |
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"r2": 0.7034275646393116,
|
| 7 |
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"pearson": 0.9094234865445358,
|
| 8 |
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"spearman": 0.7422449962055115,
|
| 9 |
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"de_corr": 0.9502354585207425,
|
| 10 |
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"mmd": 0.30546490356834105,
|
| 11 |
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"wasserstein": 0.4372436159231492,
|
| 12 |
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"_per_pert": {
|
| 13 |
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"mse": [
|
| 14 |
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0.0004416794399730861,
|
| 15 |
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| 20 |
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| 21 |
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| 22 |
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| 23 |
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| 24 |
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| 25 |
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| 26 |
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| 27 |
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| 28 |
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| 29 |
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| 30 |
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| 32 |
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| 40 |
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|
| 41 |
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| 42 |
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|
| 43 |
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| 44 |
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| 54 |
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|
| 69 |
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| 70 |
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|
| 71 |
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| 72 |
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0.9625992774963379,
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0.9880457520484924,
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| 78 |
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0.9798969030380249,
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0.8971215486526489,
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0.9108695983886719,
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| 84 |
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0.9660959243774414,
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0.9386588931083679,
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| 86 |
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0.9844915866851807,
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| 87 |
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0.9293400049209595,
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| 88 |
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0.7490290999412537,
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0.701932430267334,
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| 90 |
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0.9207367897033691,
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| 93 |
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0.8525486588478088,
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| 94 |
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| 95 |
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| 96 |
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|
| 97 |
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| 98 |
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0.40532229870442155,
|
| 99 |
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0.7695981981365192,
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| 100 |
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| 102 |
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0.7619216037663427,
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0.8265676943402535,
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0.671723228500967,
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| 108 |
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0.6946859011442998,
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| 109 |
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0.8733894077156299,
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| 110 |
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0.7313993757164831,
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| 111 |
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0.7732291276055234,
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| 112 |
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0.89247673992973,
|
| 113 |
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0.8519675614383306,
|
| 114 |
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0.8543754041910453,
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| 115 |
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0.7109876899782194,
|
| 116 |
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0.5988971571019566,
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| 117 |
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0.571165396466269,
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0.5966738634873373,
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| 119 |
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0.8095972592400602,
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| 120 |
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0.7516057058029206,
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0.7712747612701276,
|
| 122 |
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0.919446070868832,
|
| 123 |
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0.7214981469437507
|
| 124 |
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],
|
| 125 |
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"de_corr": [
|
| 126 |
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0.8499228954315186,
|
| 127 |
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0.9913710951805115,
|
| 128 |
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0.9797207117080688,
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| 129 |
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0.9553540349006653,
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0.9917449355125427,
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0.9834495186805725,
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| 133 |
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0.9824050664901733,
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| 134 |
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0.9921419620513916,
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| 1667 |
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|
| 1668 |
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}
|
| 1669 |
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}
|
experiments/results/norman_forward_perturbation.json
ADDED
|
@@ -0,0 +1,2845 @@
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| 1 |
+
{
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| 2 |
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"split": "perturbation",
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| 3 |
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"models": {
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| 4 |
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| 5 |
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|
experiments/results/norman_nom_cell.json
ADDED
|
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| 1 |
+
{
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| 2 |
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"split": "cell",
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| 3 |
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"reward": "centroid",
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| 4 |
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| 5 |
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| 6 |
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| 7 |
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| 8 |
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| 9 |
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| 10 |
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| 11 |
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| 12 |
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| 13 |
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"rank": 2.6,
|
| 14 |
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"endpoint_dist": 0.9490216635167599,
|
| 15 |
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| 16 |
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"off_dist": 2.6799996107816697,
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| 17 |
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| 18 |
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| 19 |
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| 20 |
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| 21 |
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| 61 |
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| 103 |
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experiments/results/norman_nom_improved.json
ADDED
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@@ -0,0 +1,295 @@
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| 1 |
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{
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experiments/results/norman_nom_perturbation.json
ADDED
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@@ -0,0 +1,1639 @@
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experiments/results/norman_timing_scaling.json
ADDED
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@@ -0,0 +1,89 @@
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| 89 |
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|
experiments/results/pivot_vs_gears.json
ADDED
|
@@ -0,0 +1,7 @@
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| 1 |
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| 5 |
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| 7 |
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|
experiments/results/replogle_k562_forward_cell.json
ADDED
|
The diff for this file is too large to render.
See raw diff
|
|
|
experiments/results/replogle_k562_forward_gene.json
ADDED
|
The diff for this file is too large to render.
See raw diff
|
|
|
experiments/results/replogle_k562_forward_perturbation.json
ADDED
|
The diff for this file is too large to render.
See raw diff
|
|
|
experiments/results/replogle_k562_nom_cell.json
ADDED
|
@@ -0,0 +1,2773 @@
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|
| 1 |
+
{
|
| 2 |
+
"split": "cell",
|
| 3 |
+
"reward": "centroid",
|
| 4 |
+
"n_candidates": 1805,
|
| 5 |
+
"n_targets": 40,
|
| 6 |
+
"methods": {
|
| 7 |
+
"PIVOT-ranking": {
|
| 8 |
+
"top1": 0.025,
|
| 9 |
+
"top5": 0.15,
|
| 10 |
+
"ndcg": 0.13208262047549235,
|
| 11 |
+
"func_top5": 0.725,
|
| 12 |
+
"func_ndcg": 0.3600167442071178,
|
| 13 |
+
"rank": 194.2,
|
| 14 |
+
"endpoint_dist": 1.2301450669765472,
|
| 15 |
+
"spec_margin": 1.2941597983241082,
|
| 16 |
+
"off_dist": 2.5243048638105394,
|
| 17 |
+
"clf": null,
|
| 18 |
+
"_per": {
|
| 19 |
+
"top1": [
|
| 20 |
+
0.0,
|
| 21 |
+
0.0,
|
| 22 |
+
0.0,
|
| 23 |
+
0.0,
|
| 24 |
+
0.0,
|
| 25 |
+
0.0,
|
| 26 |
+
1.0,
|
| 27 |
+
0.0,
|
| 28 |
+
0.0,
|
| 29 |
+
0.0,
|
| 30 |
+
0.0,
|
| 31 |
+
0.0,
|
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experiments/results/replogle_k562_nom_improved.json
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@@ -0,0 +1,981 @@
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| 1 |
+
{
|
| 2 |
+
"dataset": "replogle_k562",
|
| 3 |
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"split": "perturbation",
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| 4 |
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"reward": "cosine",
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| 5 |
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"n_candidates": 1805,
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| 6 |
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"n_targets": 120,
|
| 7 |
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"random_top5": 0.002770083102493075,
|
| 8 |
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"methods": {
|
| 9 |
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"PIVOT-ranking": {
|
| 10 |
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"top1": 0.0,
|
| 11 |
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"top5": 0.0,
|
| 12 |
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"ndcg": 0.0,
|
| 13 |
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"func_top5": 0.7416666666666667,
|
| 14 |
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"func_ndcg": 0.5503647310194125,
|
| 15 |
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"top5_ci": [
|
| 16 |
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0.0,
|
| 17 |
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| 18 |
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| 19 |
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],
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| 20 |
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| 21 |
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| 22 |
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| 23 |
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| 24 |
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| 25 |
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| 27 |
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| 29 |
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| 30 |
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| 31 |
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| 32 |
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| 34 |
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| 35 |
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| 37 |
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| 51 |
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| 66 |
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models/norman/config.json
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{
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"dataset": "norman",
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| 3 |
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| 4 |
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| 28 |
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| 29 |
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]
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| 30 |
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models/norman/model.ptw
ADDED
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@@ -0,0 +1,3 @@
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version https://git-lfs.github.com/spec/v1
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size 3575254
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models/norman/train_info.json
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|
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|
models/replogle_k562/config.json
ADDED
|
@@ -0,0 +1,30 @@
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|
| 1 |
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{
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| 2 |
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"dataset": "replogle_k562",
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| 3 |
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"embedding": "pca",
|
| 4 |
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"split": "cell",
|
| 5 |
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"rep_mode": "gene_op",
|
| 6 |
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"match": "batch",
|
| 7 |
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"d_pert": 64,
|
| 8 |
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"hidden": 512,
|
| 9 |
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"depth": 4,
|
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"lam_semi": 0.5,
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"lam_reg": 0.0001,
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"grad_clip": 5.0,
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"train_frac": 1.0,
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|
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| 23 |
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| 25 |
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"components": [
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| 26 |
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"map",
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| 27 |
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"tan",
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| 28 |
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"semi"
|
| 29 |
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]
|
| 30 |
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}
|
models/replogle_k562/model.ptw
ADDED
|
@@ -0,0 +1,3 @@
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version https://git-lfs.github.com/spec/v1
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oid sha256:86c51f6874ae5ddd8a9db148b643c369bb6849341f1c2a11bd72af560ab92c96
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| 3 |
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size 4010454
|
models/replogle_k562/train_info.json
ADDED
|
@@ -0,0 +1,427 @@
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|
| 313 |
+
"tan": 60.41498630077808,
|
| 314 |
+
"semi": 0.5917925590818579,
|
| 315 |
+
"reg": 0.19813017547130585,
|
| 316 |
+
"total": 70.4629694951045
|
| 317 |
+
},
|
| 318 |
+
{
|
| 319 |
+
"map": 9.708581379481725,
|
| 320 |
+
"tan": 60.503518339875455,
|
| 321 |
+
"semi": 0.5872518009953684,
|
| 322 |
+
"reg": 0.1987074689044581,
|
| 323 |
+
"total": 70.50574889740386
|
| 324 |
+
},
|
| 325 |
+
{
|
| 326 |
+
"map": 9.752153607157918,
|
| 327 |
+
"tan": 60.31089173354112,
|
| 328 |
+
"semi": 0.5835730073513923,
|
| 329 |
+
"reg": 0.19888550739783745,
|
| 330 |
+
"total": 70.3548547323648
|
| 331 |
+
},
|
| 332 |
+
{
|
| 333 |
+
"map": 9.624358759297953,
|
| 334 |
+
"tan": 60.314821961638216,
|
| 335 |
+
"semi": 0.5837421378532013,
|
| 336 |
+
"reg": 0.1992025768215006,
|
| 337 |
+
"total": 70.2310743455763
|
| 338 |
+
},
|
| 339 |
+
{
|
| 340 |
+
"map": 9.673671264153022,
|
| 341 |
+
"tan": 60.04714554625672,
|
| 342 |
+
"semi": 0.5863785871437618,
|
| 343 |
+
"reg": 0.19950627119510206,
|
| 344 |
+
"total": 70.01402956479555
|
| 345 |
+
},
|
| 346 |
+
{
|
| 347 |
+
"map": 9.601263975168203,
|
| 348 |
+
"tan": 59.98841005795962,
|
| 349 |
+
"semi": 0.582589351898664,
|
| 350 |
+
"reg": 0.19971654747987722,
|
| 351 |
+
"total": 69.88099145270013
|
| 352 |
+
},
|
| 353 |
+
{
|
| 354 |
+
"map": 9.659211703709193,
|
| 355 |
+
"tan": 60.230314973112826,
|
| 356 |
+
"semi": 0.5836410588258273,
|
| 357 |
+
"reg": 0.19984227941407787,
|
| 358 |
+
"total": 70.1813699301187
|
| 359 |
+
},
|
| 360 |
+
{
|
| 361 |
+
"map": 9.695229802812849,
|
| 362 |
+
"tan": 60.008484233509414,
|
| 363 |
+
"semi": 0.5898574017859125,
|
| 364 |
+
"reg": 0.199969258401301,
|
| 365 |
+
"total": 69.99866515320618
|
| 366 |
+
},
|
| 367 |
+
{
|
| 368 |
+
"map": 9.731371854806875,
|
| 369 |
+
"tan": 60.117312245554736,
|
| 370 |
+
"semi": 0.5865367480686733,
|
| 371 |
+
"reg": 0.20019410569946489,
|
| 372 |
+
"total": 70.14197520466594
|
| 373 |
+
},
|
| 374 |
+
{
|
| 375 |
+
"map": 9.704108560240114,
|
| 376 |
+
"tan": 60.16391328093293,
|
| 377 |
+
"semi": 0.5837481083808007,
|
| 378 |
+
"reg": 0.20012537322261117,
|
| 379 |
+
"total": 70.15991874793907
|
| 380 |
+
},
|
| 381 |
+
{
|
| 382 |
+
"map": 9.649337966720779,
|
| 383 |
+
"tan": 59.84723182777306,
|
| 384 |
+
"semi": 0.595232380675031,
|
| 385 |
+
"reg": 0.2003737132657658,
|
| 386 |
+
"total": 69.7942084770698
|
| 387 |
+
},
|
| 388 |
+
{
|
| 389 |
+
"map": 9.67079952784947,
|
| 390 |
+
"tan": 59.99238888629071,
|
| 391 |
+
"semi": 0.5785262170550111,
|
| 392 |
+
"reg": 0.20029796698650756,
|
| 393 |
+
"total": 69.95247412347175
|
| 394 |
+
},
|
| 395 |
+
{
|
| 396 |
+
"map": 9.637403655361819,
|
| 397 |
+
"tan": 59.95936525022829,
|
| 398 |
+
"semi": 0.5868523740149164,
|
| 399 |
+
"reg": 0.20019558710711344,
|
| 400 |
+
"total": 69.89021766959847
|
| 401 |
+
},
|
| 402 |
+
{
|
| 403 |
+
"map": 9.705964162752226,
|
| 404 |
+
"tan": 59.901117597307476,
|
| 405 |
+
"semi": 0.5755069797689264,
|
| 406 |
+
"reg": 0.20033776256945227,
|
| 407 |
+
"total": 69.8948581249683
|
| 408 |
+
},
|
| 409 |
+
{
|
| 410 |
+
"map": 9.650553046882926,
|
| 411 |
+
"tan": 60.12031802883396,
|
| 412 |
+
"semi": 0.5841203432578546,
|
| 413 |
+
"reg": 0.20030619087931398,
|
| 414 |
+
"total": 70.06295439484832
|
| 415 |
+
},
|
| 416 |
+
{
|
| 417 |
+
"map": 9.67817362252768,
|
| 418 |
+
"tan": 60.0385335947012,
|
| 419 |
+
"semi": 0.5809869928793474,
|
| 420 |
+
"reg": 0.20038042672268755,
|
| 421 |
+
"total": 70.00722394670758
|
| 422 |
+
}
|
| 423 |
+
],
|
| 424 |
+
"duration_s": 134.94324254989624,
|
| 425 |
+
"device": "cuda:3",
|
| 426 |
+
"n_train_cells": 78128
|
| 427 |
+
}
|
requirements.txt
ADDED
|
@@ -0,0 +1,12 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
torch>=2.0
|
| 2 |
+
numpy
|
| 3 |
+
scipy
|
| 4 |
+
scikit-learn
|
| 5 |
+
pandas
|
| 6 |
+
pyarrow
|
| 7 |
+
scanpy
|
| 8 |
+
anndata
|
| 9 |
+
matplotlib
|
| 10 |
+
|
| 11 |
+
# gears is only needed for the head-to-head baseline and lives in a separate env
|
| 12 |
+
# (see scripts/setup_gears_env.sh) because it pins older torch/pyg versions.
|
scripts/extra_ablations.py
ADDED
|
@@ -0,0 +1,110 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
"""extra experiments to fill in the runnable table cells. external methods we
|
| 2 |
+
can't reproduce stay unreported; only real computed values get emitted."""
|
| 3 |
+
import sys, os, json, time
|
| 4 |
+
sys.path.insert(0, os.path.abspath(os.path.join(os.path.dirname(__file__), "..")))
|
| 5 |
+
import numpy as np, torch
|
| 6 |
+
from src.data.perturb_data import load_dataset
|
| 7 |
+
from src.data.splits import load_split
|
| 8 |
+
from src.training.train import TrainConfig, train
|
| 9 |
+
from src.experiments.predictors import PivotPredictor, BaselinePredictor
|
| 10 |
+
from src.experiments.forward_eval import evaluate_forward
|
| 11 |
+
from src.experiments.nomination_eval import evaluate_nomination
|
| 12 |
+
from src.evaluation.baselines import build_baseline
|
| 13 |
+
from src.utils.common import save_json
|
| 14 |
+
|
| 15 |
+
gpu = int(os.environ.get("PIVOT_GPU", "3"))
|
| 16 |
+
data = load_dataset("norman")
|
| 17 |
+
out = {}
|
| 18 |
+
|
| 19 |
+
# ===== core-ablation extras (centroid reward, held-out perturbation) =====
|
| 20 |
+
sp = load_split(data.dir, "perturbation")
|
| 21 |
+
cands = [p for p in data.perturbations if len(data.parse(p)) == 1]
|
| 22 |
+
targets = [p for p in sp["test_perts"] if len(data.parse(p)) == 1 and p in cands][:30]
|
| 23 |
+
gc = data.functional_clusters(seed=0)
|
| 24 |
+
|
| 25 |
+
def fwd_inv(model, reward="centroid"):
|
| 26 |
+
dev = next(model.parameters()).device
|
| 27 |
+
pred = PivotPredictor(model, data, dev)
|
| 28 |
+
f = evaluate_forward(pred, data, list(sp["test_perts"])[:50], data.control_idx, max_perts=50)
|
| 29 |
+
r = evaluate_nomination(pred, data, targets, cands, data.control_idx, reward_kind=reward,
|
| 30 |
+
method="ranking", gene_cluster=gc, device=dev)
|
| 31 |
+
g = evaluate_nomination(pred, data, targets, cands, data.control_idx, reward_kind=reward,
|
| 32 |
+
method="guidance", guidance_init="warm", rerank=False,
|
| 33 |
+
gene_cluster=gc, model=model, device=dev)
|
| 34 |
+
return f, r, g
|
| 35 |
+
|
| 36 |
+
# velocity-only: train with only the tangent (velocity) loss
|
| 37 |
+
mv, _ = train(TrainConfig(dataset="norman", split="perturbation", epochs=60, device_index=gpu,
|
| 38 |
+
components=["tan"]), data=data, verbose=False)
|
| 39 |
+
fv, rv, _ = fwd_inv(mv)
|
| 40 |
+
out["velocity_only"] = {"mse": fv["mse"], "de_corr": fv["de_corr"], "mmd": fv["mmd"],
|
| 41 |
+
"endpoint_dist": rv["endpoint_dist"], "top5": rv["top5"], "ndcg": rv["ndcg"]}
|
| 42 |
+
print("velocity_only", out["velocity_only"], flush=True)
|
| 43 |
+
|
| 44 |
+
# full model: ranking-only and guidance-without-reranking inverse rows
|
| 45 |
+
mf, info = train(TrainConfig(dataset="norman", split="perturbation", epochs=60, device_index=gpu),
|
| 46 |
+
data=data, verbose=False)
|
| 47 |
+
dev = next(mf.parameters()).device
|
| 48 |
+
ff, rf, gf = fwd_inv(mf)
|
| 49 |
+
out["ranking_only"] = {"mse": ff["mse"], "de_corr": ff["de_corr"], "mmd": ff["mmd"],
|
| 50 |
+
"endpoint_dist": rf["endpoint_dist"], "top5": rf["top5"], "ndcg": rf["ndcg"]}
|
| 51 |
+
out["guidance_no_rerank"] = {"mse": ff["mse"], "de_corr": ff["de_corr"], "mmd": ff["mmd"],
|
| 52 |
+
"endpoint_dist": gf["endpoint_dist"], "top5": gf["top5"], "ndcg": gf["ndcg"]}
|
| 53 |
+
print("ranking_only", out["ranking_only"], flush=True)
|
| 54 |
+
print("guidance_no_rerank", out["guidance_no_rerank"], flush=True)
|
| 55 |
+
|
| 56 |
+
# ===== inverse-table baseline: average perturbation effect + ranking (cosine) =====
|
| 57 |
+
bl = BaselinePredictor(build_baseline("AvgPerturbationEffect").fit(data, sp["train_perts"], sp["train_idx"]))
|
| 58 |
+
ra = evaluate_nomination(bl, data, targets, cands, data.control_idx, reward_kind="cosine",
|
| 59 |
+
method="ranking", gene_cluster=gc, device=dev)
|
| 60 |
+
out["avg_effect_ranking"] = {k: ra[k] for k in ["top1", "top5", "ndcg", "func_top5"]}
|
| 61 |
+
out["avg_effect_ranking"]["med_rank"] = float(np.median(ra["_per"]["rank"]))
|
| 62 |
+
print("avg_effect_ranking", out["avg_effect_ranking"], flush=True)
|
| 63 |
+
|
| 64 |
+
# ===== gpu memory for compute table =====
|
| 65 |
+
torch.cuda.reset_peak_memory_stats(dev)
|
| 66 |
+
c0 = torch.as_tensor(data.emb[data.control_idx[:256]], dtype=torch.float32, device=dev)
|
| 67 |
+
from src.evaluation import inference as inf
|
| 68 |
+
_ = inf.endpoint_ranking(mf, data, cands, c0, __import__("src.evaluation.rewards", fromlist=["Reward"]).Reward(
|
| 69 |
+
"centroid", target_c=data.emb[data.pert_to_idx[targets[0]]].mean(0), device=dev), device=dev)
|
| 70 |
+
out["gpu_mem_mb"] = round(torch.cuda.max_memory_allocated(dev) / 1e6, 1)
|
| 71 |
+
print("gpu_mem_mb", out["gpu_mem_mb"], flush=True)
|
| 72 |
+
|
| 73 |
+
# ===== combination table: additive + random + pivot guidance (combination split) =====
|
| 74 |
+
spc = load_split(data.dir, "combination")
|
| 75 |
+
combo_cands = data.combos
|
| 76 |
+
ctgt = [p for p in spc["test_perts"] if len(data.parse(p)) == 2][:26]
|
| 77 |
+
mc, _ = train(TrainConfig(dataset="norman", split="combination", epochs=60, device_index=gpu),
|
| 78 |
+
data=data, verbose=False)
|
| 79 |
+
devc = next(mc.parameters()).device
|
| 80 |
+
predc = PivotPredictor(mc, data, devc)
|
| 81 |
+
from src.experiments.nomination_eval import rank_candidates
|
| 82 |
+
import src.evaluation.metrics as M
|
| 83 |
+
rng = np.random.default_rng(0)
|
| 84 |
+
# additive baseline ranking over observed combos
|
| 85 |
+
addb = build_baseline("Additive").fit(data, spc["train_perts"], spc["train_idx"])
|
| 86 |
+
addp = BaselinePredictor(addb)
|
| 87 |
+
def combo_eval(predictor):
|
| 88 |
+
e1=e5=ov=0.0
|
| 89 |
+
for p in ctgt:
|
| 90 |
+
cstar = data.emb[data.pert_to_idx[p]].mean(0)
|
| 91 |
+
c0n = data.emb[rng.choice(data.control_idx, 128, replace=False)]
|
| 92 |
+
sk = dict(kind="centroid", c_star=cstar, target_sample=data.emb[data.pert_to_idx[p]],
|
| 93 |
+
device=devc, control_ref=data.emb[data.control_idx].mean(0))
|
| 94 |
+
ranked,_ = rank_candidates(predictor, combo_cands, c0n, sk)
|
| 95 |
+
e1 += M.top_k_accuracy(ranked,p,1); e5 += M.top_k_accuracy(ranked,p,5)
|
| 96 |
+
ov += M.partial_overlap(data.parse(ranked[0]), set(data.parse(p)))
|
| 97 |
+
n=len(ctgt); return e1/n, e5/n, ov/n
|
| 98 |
+
ae1, ae5, aov = combo_eval(addp)
|
| 99 |
+
out["combo_additive"] = {"exact1": ae1, "exact5": ae5, "overlap": aov}
|
| 100 |
+
# random combos
|
| 101 |
+
r_e1=r_e5=r_ov=0.0
|
| 102 |
+
for p in ctgt:
|
| 103 |
+
pick = list(rng.choice(combo_cands, 5, replace=False))
|
| 104 |
+
r_e1 += float(p==pick[0]); r_e5 += float(p in pick)
|
| 105 |
+
r_ov += M.partial_overlap(data.parse(pick[0]), set(data.parse(p)))
|
| 106 |
+
n=len(ctgt); out["combo_random"]={"exact1":r_e1/n,"exact5":r_e5/n,"overlap":r_ov/n}
|
| 107 |
+
print("combo_additive", out["combo_additive"], "combo_random", out["combo_random"], flush=True)
|
| 108 |
+
|
| 109 |
+
save_json(out, "experiments/results/norman_extra_ablations.json")
|
| 110 |
+
print("FILL_DONE", flush=True)
|
scripts/figures.py
ADDED
|
@@ -0,0 +1,172 @@
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
| 1 |
+
"""figures for the paper, helvetica-ish font (nimbus sans).
|
| 2 |
+
figure 1: effect-axis embedding panels (control / observed / pivot-predicted).
|
| 3 |
+
figure 2: quantitative results (forward bars, gears head-to-head, dist-loss, reward)."""
|
| 4 |
+
import sys, os, glob, json
|
| 5 |
+
sys.path.insert(0, os.path.abspath(os.path.join(os.path.dirname(__file__), "..")))
|
| 6 |
+
import numpy as np
|
| 7 |
+
import matplotlib
|
| 8 |
+
matplotlib.use("Agg")
|
| 9 |
+
from matplotlib import font_manager as fm
|
| 10 |
+
import matplotlib.pyplot as plt
|
| 11 |
+
from matplotlib.patches import Patch
|
| 12 |
+
from matplotlib.lines import Line2D
|
| 13 |
+
|
| 14 |
+
# helvetica-family font (nimbus sans = urw helvetica clone)
|
| 15 |
+
for patt in ["/usr/share/fonts/opentype/urw-base35/NimbusSans-*.otf",
|
| 16 |
+
"/usr/share/fonts/truetype/liberation2/LiberationSans-*.ttf"]:
|
| 17 |
+
for f in glob.glob(patt):
|
| 18 |
+
try: fm.fontManager.addfont(f)
|
| 19 |
+
except Exception: pass
|
| 20 |
+
plt.rcParams.update({
|
| 21 |
+
"font.family": "sans-serif",
|
| 22 |
+
"font.sans-serif": ["Nimbus Sans", "Helvetica", "Arial", "Liberation Sans", "DejaVu Sans"],
|
| 23 |
+
"mathtext.fontset": "dejavusans",
|
| 24 |
+
"font.size": 11, "axes.labelsize": 12, "axes.titlesize": 12.5,
|
| 25 |
+
"xtick.labelsize": 10, "ytick.labelsize": 10, "legend.fontsize": 10,
|
| 26 |
+
"axes.linewidth": 0.9, "axes.edgecolor": "#444444",
|
| 27 |
+
"xtick.color": "#444444", "ytick.color": "#444444",
|
| 28 |
+
"axes.labelcolor": "#222222", "text.color": "#222222",
|
| 29 |
+
"figure.dpi": 150, "savefig.dpi": 320, "savefig.bbox": "tight",
|
| 30 |
+
"axes.spines.top": False, "axes.spines.right": False,
|
| 31 |
+
"axes.grid": True, "grid.color": "#E6E8EB", "grid.linewidth": 0.8,
|
| 32 |
+
"axes.axisbelow": True, "legend.frameon": False,
|
| 33 |
+
})
|
| 34 |
+
# palette
|
| 35 |
+
C_CTRL, C_OBS, C_PRED, C_PIVOT, C_BASE, C_ACC = "#B9C2CC", "#2D6FB3", "#E4572E", "#1B9E77", "#9AA6B2", "#6A4C93"
|
| 36 |
+
FIG = "figures"
|
| 37 |
+
RES = "experiments/results"
|
| 38 |
+
os.makedirs(FIG, exist_ok=True)
|
| 39 |
+
def L(n): return json.load(open(f"{RES}/{n}.json"))
|
| 40 |
+
def save(fig, name):
|
| 41 |
+
fig.savefig(f"{FIG}/{name}.png"); fig.savefig(f"{FIG}/{name}.pdf"); plt.close(fig)
|
| 42 |
+
print("wrote", name)
|
| 43 |
+
|
| 44 |
+
|
| 45 |
+
def kde_contour(ax, X, color, levels=4):
|
| 46 |
+
try:
|
| 47 |
+
from scipy.stats import gaussian_kde
|
| 48 |
+
if len(X) < 10: return
|
| 49 |
+
k = gaussian_kde(X.T)
|
| 50 |
+
xmin, ymin = X.min(0); xmax, ymax = X.max(0)
|
| 51 |
+
xs, ys = np.mgrid[xmin:xmax:80j, ymin:ymax:80j]
|
| 52 |
+
z = k(np.vstack([xs.ravel(), ys.ravel()])).reshape(xs.shape)
|
| 53 |
+
ax.contour(xs, ys, z, levels=levels, colors=color, linewidths=1.0, alpha=0.55)
|
| 54 |
+
except Exception:
|
| 55 |
+
pass
|
| 56 |
+
|
| 57 |
+
|
| 58 |
+
def figure1(model, data, targets, device):
|
| 59 |
+
"""effect-axis panels: x = projection on (target-control) direction, y = orthogonal pc."""
|
| 60 |
+
from src.evaluation import inference as inf
|
| 61 |
+
import torch
|
| 62 |
+
rng = np.random.default_rng(0)
|
| 63 |
+
ctrl_idx = data.control_idx
|
| 64 |
+
cmean = data.emb[ctrl_idx].mean(0)
|
| 65 |
+
c0e = torch.as_tensor(data.emb[rng.choice(ctrl_idx, 400, replace=False)], dtype=torch.float32, device=device)
|
| 66 |
+
n = len(targets)
|
| 67 |
+
fig, axes = plt.subplots(1, n, figsize=(4.3 * n, 4.1))
|
| 68 |
+
if n == 1: axes = [axes]
|
| 69 |
+
for ax, p in zip(axes, targets):
|
| 70 |
+
ti = data.pert_to_idx[p]
|
| 71 |
+
tmean = data.emb[ti].mean(0)
|
| 72 |
+
d = tmean - cmean; d = d / (np.linalg.norm(d) + 1e-9) # effect direction
|
| 73 |
+
# orthogonal axis = top pc of perturbed cells with effect-dir removed
|
| 74 |
+
Y = data.emb[ti] - data.emb[ti].mean(0)
|
| 75 |
+
Y = Y - np.outer(Y @ d, d)
|
| 76 |
+
u, s, vt = np.linalg.svd(Y, full_matrices=False); o = vt[0]
|
| 77 |
+
def proj(M): return np.c_[(M - cmean) @ d, (M - cmean) @ o]
|
| 78 |
+
ci = rng.choice(ctrl_idx, 500, replace=False)
|
| 79 |
+
Pc, Po = proj(data.emb[ci]), proj(data.emb[ti])
|
| 80 |
+
e = inf.encode_label(model, data, p, device)
|
| 81 |
+
Ppred = proj(inf.forward_predict(model, c0e, e).cpu().numpy())
|
| 82 |
+
ax.scatter(Pc[:, 0], Pc[:, 1], s=9, c=C_CTRL, alpha=0.7, linewidths=0, label="control", rasterized=True)
|
| 83 |
+
ax.scatter(Po[:, 0], Po[:, 1], s=11, c=C_OBS, alpha=0.55, linewidths=0, label="observed perturbed", rasterized=True)
|
| 84 |
+
ax.scatter(Ppred[:, 0], Ppred[:, 1], s=22, marker="X", c=C_PRED, alpha=0.9,
|
| 85 |
+
edgecolors="white", linewidths=0.4, label="PIVOT predicted")
|
| 86 |
+
kde_contour(ax, Po, C_OBS); kde_contour(ax, Ppred, C_PRED)
|
| 87 |
+
# arrow control-centroid -> observed-centroid (the transport)
|
| 88 |
+
cc, oc = proj(cmean[None])[0], proj(tmean[None])[0]
|
| 89 |
+
ax.annotate("", xy=(oc[0], oc[1]), xytext=(cc[0], cc[1]),
|
| 90 |
+
arrowprops=dict(arrowstyle="-|>", color="#333333", lw=1.6, alpha=0.8))
|
| 91 |
+
ax.set_title(p.replace("_", "+"), fontweight="bold")
|
| 92 |
+
ax.set_xlabel("effect axis"); ax.set_ylabel("orthogonal axis")
|
| 93 |
+
ax.tick_params(length=0)
|
| 94 |
+
handles = [Line2D([], [], marker='o', ls='', mfc=C_CTRL, mec='none', ms=7, label='control'),
|
| 95 |
+
Line2D([], [], marker='o', ls='', mfc=C_OBS, mec='none', ms=7, label='observed perturbed'),
|
| 96 |
+
Line2D([], [], marker='X', ls='', mfc=C_PRED, mec='white', ms=8, label='PIVOT predicted')]
|
| 97 |
+
fig.legend(handles=handles, loc="lower center", ncol=3, bbox_to_anchor=(0.5, -0.04))
|
| 98 |
+
fig.suptitle("Control cells transported toward the perturbed population", y=1.02,
|
| 99 |
+
fontsize=13, fontweight="bold")
|
| 100 |
+
fig.tight_layout()
|
| 101 |
+
save(fig, "fig1_embedding_panels")
|
| 102 |
+
|
| 103 |
+
|
| 104 |
+
def figure2_results():
|
| 105 |
+
fig, ax = plt.subplots(2, 2, figsize=(11, 7.4))
|
| 106 |
+
# (a) forward de-corr across methods (held-out perturbation), from benchmark
|
| 107 |
+
bf = L("norman_benchmark")["forward"]
|
| 108 |
+
order = ["PIVOT", "LinearResponse", "kNN-latent", "Additive", "NearestPerturbationCentroid",
|
| 109 |
+
"ConditionalMLP", "EndpointMLP", "AvgPerturbationEffect", "MeanControl", "Random"]
|
| 110 |
+
pretty = {"PIVOT": "PIVOT", "LinearResponse": "Linear", "kNN-latent": "kNN-latent",
|
| 111 |
+
"Additive": "Additive", "NearestPerturbationCentroid": "Nearest centroid",
|
| 112 |
+
"ConditionalMLP": "Conditional MLP", "EndpointMLP": "Endpoint MLP",
|
| 113 |
+
"AvgPerturbationEffect": "Avg. effect", "MeanControl": "Mean control", "Random": "Random"}
|
| 114 |
+
vals = [(pretty[m], bf[m]["de_corr"]) for m in order if m in bf]
|
| 115 |
+
vals.sort(key=lambda kv: kv[1])
|
| 116 |
+
names = [v[0] for v in vals]; de = [v[1] for v in vals]
|
| 117 |
+
cols = [C_PIVOT if n == "PIVOT" else C_BASE for n in names]
|
| 118 |
+
a = ax[0, 0]; a.barh(names, de, color=cols, edgecolor="white", height=0.74)
|
| 119 |
+
for i, v in enumerate(de): a.text(v + 0.01, i, f"{v:.2f}", va="center", fontsize=9, color="#333")
|
| 120 |
+
a.set_xlim(0, 1.0); a.set_xlabel("DE correlation $\\uparrow$"); a.grid(axis="y", visible=False)
|
| 121 |
+
a.set_title("a Forward direction, held-out perturbations", loc="left", fontweight="bold")
|
| 122 |
+
|
| 123 |
+
# (b) gears head-to-head
|
| 124 |
+
pg = L("pivot_vs_gears")
|
| 125 |
+
b = ax[0, 1]
|
| 126 |
+
bars = b.bar(["PIVOT", "GEARS"], [pg["pivot_pearson_de_expr"], pg["gears_pearson_de_expr"]],
|
| 127 |
+
color=[C_PIVOT, C_ACC], edgecolor="white", width=0.55)
|
| 128 |
+
for r, v in zip(bars, [pg["pivot_pearson_de_expr"], pg["gears_pearson_de_expr"]]):
|
| 129 |
+
b.text(r.get_x() + r.get_width()/2, v + 0.012, f"{v:.3f}", ha="center", fontsize=11, fontweight="bold")
|
| 130 |
+
b.set_ylim(0, 1.08); b.set_ylabel("Top-20 DE-gene Pearson $\\uparrow$"); b.grid(axis="x", visible=False)
|
| 131 |
+
b.set_title("b Head-to-head vs GEARS (matched perts)", loc="left", fontweight="bold")
|
| 132 |
+
|
| 133 |
+
# (c) distributional loss: mmd down, de-corr preserved
|
| 134 |
+
dl = L("norman_distloss")["rows"]
|
| 135 |
+
lam = sorted(float(k) for k in dl); mmd = [dl[str(l) if str(l) in dl else f"{l:.1f}"]["mmd"] for l in lam]
|
| 136 |
+
de2 = [dl[str(l) if str(l) in dl else f"{l:.1f}"]["de_corr"] for l in lam]
|
| 137 |
+
c = ax[1, 0]
|
| 138 |
+
c.plot(lam, mmd, "o-", color=C_PRED, lw=2.2, ms=7, label="MMD $\\downarrow$")
|
| 139 |
+
c.set_xlabel("distributional-loss weight $\\lambda_{\\mathrm{dist}}$"); c.set_ylabel("population MMD $\\downarrow$", color=C_PRED)
|
| 140 |
+
c.tick_params(axis="y", colors=C_PRED); c.set_ylim(0, max(mmd)*1.15)
|
| 141 |
+
c2 = c.twinx(); c2.plot(lam, de2, "s--", color=C_OBS, lw=2.0, ms=6, label="DE-corr $\\uparrow$")
|
| 142 |
+
c2.set_ylabel("DE correlation $\\uparrow$", color=C_OBS); c2.tick_params(axis="y", colors=C_OBS)
|
| 143 |
+
c2.set_ylim(0.5, 0.95); c2.grid(False); c2.spines["top"].set_visible(False)
|
| 144 |
+
c.set_title("c Distributional flow loss: MMD $6\\times$ lower, direction kept", loc="left", fontweight="bold")
|
| 145 |
+
|
| 146 |
+
# (d) reward ablation top-5
|
| 147 |
+
rw = L("norman_ablation_reward")["rows"]
|
| 148 |
+
rmap = {"centroid": "Centroid", "nn_target": "NN-target", "mmd": "MMD", "wasserstein": "Wasserstein", "cosine": "Cosine"}
|
| 149 |
+
rn = [rmap.get(k, k) for k in rw]; t5 = [rw[k]["top5"] for k in rw]
|
| 150 |
+
cols2 = [C_PIVOT if rmap.get(k) == "Cosine" else C_BASE for k in rw]
|
| 151 |
+
d = ax[1, 1]; bars = d.bar(rn, t5, color=cols2, edgecolor="white", width=0.66)
|
| 152 |
+
for r, v in zip(bars, t5): d.text(r.get_x()+r.get_width()/2, v+0.006, f"{v:.2f}", ha="center", fontsize=9.5)
|
| 153 |
+
d.set_ylabel("nomination Top-5 $\\uparrow$"); d.set_ylim(0, max(t5)*1.25); d.grid(axis="x", visible=False)
|
| 154 |
+
d.tick_params(axis="x", rotation=18)
|
| 155 |
+
d.set_title("d Direction-aware reward wins at nomination", loc="left", fontweight="bold")
|
| 156 |
+
fig.tight_layout()
|
| 157 |
+
save(fig, "fig2_results")
|
| 158 |
+
|
| 159 |
+
|
| 160 |
+
if __name__ == "__main__":
|
| 161 |
+
from src.data.perturb_data import load_dataset
|
| 162 |
+
from src.training.train import TrainConfig, train
|
| 163 |
+
data = load_dataset("norman")
|
| 164 |
+
gpu = int(os.environ.get("PIVOT_GPU", "3"))
|
| 165 |
+
cfg = TrainConfig(dataset="norman", split="cell", epochs=60, device_index=gpu)
|
| 166 |
+
model, info = train(cfg, data=data, verbose=False)
|
| 167 |
+
dev = next(model.parameters()).device
|
| 168 |
+
singles = [p for p in data.perturbations if len(data.parse(p)) == 1]
|
| 169 |
+
combos = [p for p in data.perturbations if len(data.parse(p)) == 2]
|
| 170 |
+
figure1(model, data, [singles[0], singles[7], combos[0]], dev)
|
| 171 |
+
figure2_results()
|
| 172 |
+
print("FIGURES_V2_DONE")
|
scripts/gears_compare.py
ADDED
|
@@ -0,0 +1,58 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
"""real gears head-to-head on norman, aligned to our held-out-perturbation test set.
|
| 2 |
+
runs in the isolated pivot_gears env (torch cu118 + pyg + cell-gears, gpu-capable)."""
|
| 3 |
+
import sys, os, json
|
| 4 |
+
import numpy as np
|
| 5 |
+
import torch
|
| 6 |
+
|
| 7 |
+
# our held-out perturbation test labels (no src import; read the npz directly)
|
| 8 |
+
split = np.load("data/processed/norman/splits/perturbation.npz", allow_pickle=True)
|
| 9 |
+
my_test = [str(p) for p in split["test_perts"]]
|
| 10 |
+
|
| 11 |
+
def to_gears(p):
|
| 12 |
+
g = [x for x in p.split("_") if x]
|
| 13 |
+
return g[0] + "+ctrl" if len(g) == 1 else g[0] + "+" + g[1]
|
| 14 |
+
|
| 15 |
+
import pickle
|
| 16 |
+
from gears import PertData, GEARS
|
| 17 |
+
from gears.inference import evaluate, compute_metrics
|
| 18 |
+
|
| 19 |
+
my_train = [str(p) for p in np.load("data/processed/norman/splits/perturbation.npz",
|
| 20 |
+
allow_pickle=True)["train_perts"]]
|
| 21 |
+
dev = "cuda"
|
| 22 |
+
pert_data = PertData("./gears_data")
|
| 23 |
+
pert_data.load(data_name="norman")
|
| 24 |
+
avail = set(map(str, pert_data.adata.obs["condition"].unique()))
|
| 25 |
+
print("example GEARS conditions:", list(avail)[:6], flush=True)
|
| 26 |
+
gears_test = sorted({to_gears(p) for p in my_test} & avail)
|
| 27 |
+
gears_train = sorted(({to_gears(p) for p in my_train} & avail) - set(gears_test))
|
| 28 |
+
if "ctrl" in avail:
|
| 29 |
+
gears_train = sorted(set(gears_train) | {"ctrl"})
|
| 30 |
+
# carve a small val set from train (gears requires non-empty val)
|
| 31 |
+
rng = np.random.default_rng(0)
|
| 32 |
+
val = sorted(rng.choice([c for c in gears_train if c != "ctrl"],
|
| 33 |
+
size=max(1, len(gears_train) // 10), replace=False).tolist())
|
| 34 |
+
gears_train = sorted(set(gears_train) - set(val))
|
| 35 |
+
split_dict = {"train": gears_train, "val": val, "test": gears_test}
|
| 36 |
+
print(f"custom split -> train {len(gears_train)} | val {len(val)} | test {len(gears_test)} "
|
| 37 |
+
f"(our test {len(my_test)})", flush=True)
|
| 38 |
+
os.makedirs("gears_data", exist_ok=True)
|
| 39 |
+
sd_path = "gears_data/pivot_custom_split.pkl"
|
| 40 |
+
pickle.dump(split_dict, open(sd_path, "wb"))
|
| 41 |
+
pert_data.prepare_split(split="custom", split_dict_path=sd_path)
|
| 42 |
+
pert_data.get_dataloader(batch_size=64, test_batch_size=128)
|
| 43 |
+
|
| 44 |
+
model = GEARS(pert_data, device=dev)
|
| 45 |
+
model.model_initialize(hidden_size=64)
|
| 46 |
+
model.train(epochs=20)
|
| 47 |
+
|
| 48 |
+
res = evaluate(pert_data.dataloader["test_loader"], model.model, False, dev)
|
| 49 |
+
out = compute_metrics(res)
|
| 50 |
+
metrics, per_pert = out if isinstance(out, tuple) else (out, {})
|
| 51 |
+
keep = {k: float(v) for k, v in metrics.items()
|
| 52 |
+
if any(s in k for s in ["pearson", "mse", "r2", "spearman"])}
|
| 53 |
+
print("GEARS held-out-perturbation metrics:", flush=True)
|
| 54 |
+
for k, v in sorted(keep.items()):
|
| 55 |
+
print(f" {k:24s} {v:.4f}", flush=True)
|
| 56 |
+
json.dump({"n_test_perts": len(gears_test), "test_perts": gears_test, "metrics": keep},
|
| 57 |
+
open("experiments/results/gears_norman.json", "w"), indent=2, default=float)
|
| 58 |
+
print("GEARS_RUN_DONE", flush=True)
|
scripts/gears_ranking.py
ADDED
|
@@ -0,0 +1,144 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
"""gears + ranking baseline for inverse nomination, done entirely in gears' native
|
| 2 |
+
gene space (fair: top-k recovery is representation-agnostic). trains gears on our
|
| 3 |
+
held-out-perturbation split, predicts post-perturbation expression for every
|
| 4 |
+
candidate, and ranks candidates by l2 distance to each held-out target's true mean
|
| 5 |
+
expression. emits top-1/5, ndcg@10, median rank for single-gene and combination
|
| 6 |
+
targets. runs in the isolated pivot_gears env."""
|
| 7 |
+
import os, json, pickle
|
| 8 |
+
import numpy as np
|
| 9 |
+
|
| 10 |
+
PROC = "data/processed/norman"
|
| 11 |
+
split = np.load(f"{PROC}/splits/perturbation.npz", allow_pickle=True)
|
| 12 |
+
splitC = np.load(f"{PROC}/splits/combination.npz", allow_pickle=True)
|
| 13 |
+
my_test = [str(p) for p in split["test_perts"]]
|
| 14 |
+
my_train = [str(p) for p in split["train_perts"]]
|
| 15 |
+
combo_test = [str(p) for p in splitC["test_perts"]]
|
| 16 |
+
|
| 17 |
+
|
| 18 |
+
def to_gears(p):
|
| 19 |
+
g = [x for x in p.split("_") if x]
|
| 20 |
+
return g[0] + "+ctrl" if len(g) == 1 else g[0] + "+" + g[1]
|
| 21 |
+
|
| 22 |
+
|
| 23 |
+
def ndcg_at_k(ranked, true, k=10):
|
| 24 |
+
rel = [1.0 if r == true else 0.0 for r in ranked[:k]]
|
| 25 |
+
dcg = sum(r / np.log2(i + 2) for i, r in enumerate(rel))
|
| 26 |
+
return float(dcg) # ideal dcg = 1 (single relevant) -> ndcg = dcg
|
| 27 |
+
|
| 28 |
+
|
| 29 |
+
from gears import PertData, GEARS
|
| 30 |
+
|
| 31 |
+
dev = "cuda"
|
| 32 |
+
pert_data = PertData("./gears_data")
|
| 33 |
+
pert_data.load(data_name="norman")
|
| 34 |
+
avail = set(map(str, pert_data.adata.obs["condition"].unique()))
|
| 35 |
+
gears_test = sorted({to_gears(p) for p in my_test} & avail)
|
| 36 |
+
gears_train = sorted(({to_gears(p) for p in my_train} & avail) - set(gears_test))
|
| 37 |
+
if "ctrl" in avail:
|
| 38 |
+
gears_train = sorted(set(gears_train) | {"ctrl"})
|
| 39 |
+
rng = np.random.default_rng(0)
|
| 40 |
+
val = sorted(rng.choice([c for c in gears_train if c != "ctrl"],
|
| 41 |
+
size=max(1, len(gears_train) // 10), replace=False).tolist())
|
| 42 |
+
gears_train = sorted(set(gears_train) - set(val))
|
| 43 |
+
split_dict = {"train": gears_train, "val": val, "test": gears_test}
|
| 44 |
+
os.makedirs("gears_data", exist_ok=True)
|
| 45 |
+
pickle.dump(split_dict, open("gears_data/pivot_custom_split.pkl", "wb"))
|
| 46 |
+
pert_data.prepare_split(split="custom", split_dict_path="gears_data/pivot_custom_split.pkl")
|
| 47 |
+
pert_data.get_dataloader(batch_size=64, test_batch_size=128)
|
| 48 |
+
|
| 49 |
+
model = GEARS(pert_data, device=dev)
|
| 50 |
+
model.model_initialize(hidden_size=64)
|
| 51 |
+
model.train(epochs=20)
|
| 52 |
+
print("GEARS trained", flush=True)
|
| 53 |
+
|
| 54 |
+
adata = pert_data.adata
|
| 55 |
+
genes = list(adata.var["gene_name"]) if "gene_name" in adata.var else list(adata.var_names)
|
| 56 |
+
cond = adata.obs["condition"].astype(str).values
|
| 57 |
+
X = adata.X
|
| 58 |
+
X = np.asarray(X.todense()) if hasattr(X, "todense") else np.asarray(X)
|
| 59 |
+
|
| 60 |
+
|
| 61 |
+
def true_mean(gcond):
|
| 62 |
+
m = cond == gcond
|
| 63 |
+
return X[m].mean(0) if m.sum() else None
|
| 64 |
+
|
| 65 |
+
|
| 66 |
+
# candidate single genes present in gears as "GENE+ctrl"
|
| 67 |
+
single_conds = sorted([c for c in avail if c.endswith("+ctrl") and c != "ctrl"])
|
| 68 |
+
single_genes = [c.split("+")[0] for c in single_conds]
|
| 69 |
+
# predict every candidate's post-perturbation expression (gene space)
|
| 70 |
+
pred = {}
|
| 71 |
+
B = 64
|
| 72 |
+
for i in range(0, len(single_genes), B):
|
| 73 |
+
chunk = single_genes[i:i + B]
|
| 74 |
+
try:
|
| 75 |
+
out = model.predict([[g] for g in chunk])
|
| 76 |
+
except Exception as e:
|
| 77 |
+
print("predict chunk failed", chunk[:3], e, flush=True)
|
| 78 |
+
out = {}
|
| 79 |
+
for g in chunk:
|
| 80 |
+
for key in (g, g + "+ctrl", "_".join([g])):
|
| 81 |
+
if key in out:
|
| 82 |
+
pred[g] = np.asarray(out[key]); break
|
| 83 |
+
print(f"predicted {len(pred)}/{len(single_genes)} single candidates", flush=True)
|
| 84 |
+
|
| 85 |
+
cand_genes = [g for g in single_genes if g in pred]
|
| 86 |
+
P = np.stack([pred[g] for g in cand_genes]) # [n_cand, n_genes]
|
| 87 |
+
|
| 88 |
+
# single-gene targets (held-out), matched to pivot singles
|
| 89 |
+
single_targets = [t for t in my_test if "_" not in t and to_gears(t).split("+")[0] in pred]
|
| 90 |
+
res = {"single": {"top1": [], "top5": [], "ndcg": [], "rank": []}}
|
| 91 |
+
for t in single_targets:
|
| 92 |
+
tg = to_gears(t)
|
| 93 |
+
tm = true_mean(tg)
|
| 94 |
+
if tm is None:
|
| 95 |
+
continue
|
| 96 |
+
d = np.linalg.norm(P - tm[None], axis=1)
|
| 97 |
+
order = [cand_genes[i] for i in np.argsort(d)]
|
| 98 |
+
tgene = tg.split("+")[0]
|
| 99 |
+
res["single"]["top1"].append(float(order[0] == tgene))
|
| 100 |
+
res["single"]["top5"].append(float(tgene in order[:5]))
|
| 101 |
+
res["single"]["ndcg"].append(ndcg_at_k(order, tgene, 10))
|
| 102 |
+
res["single"]["rank"].append(int(order.index(tgene) + 1) if tgene in order else len(order))
|
| 103 |
+
|
| 104 |
+
# combination targets: predict combos and rank among observed combos
|
| 105 |
+
combo_conds = sorted([c for c in avail if c.count("+") == 1 and "ctrl" not in c])
|
| 106 |
+
cpred = {}
|
| 107 |
+
for i in range(0, len(combo_conds), B):
|
| 108 |
+
chunk = combo_conds[i:i + B]
|
| 109 |
+
try:
|
| 110 |
+
out = model.predict([c.split("+") for c in chunk])
|
| 111 |
+
except Exception as e:
|
| 112 |
+
print("combo predict failed", e, flush=True); out = {}
|
| 113 |
+
for c in chunk:
|
| 114 |
+
for key in (c, c.replace("+", "_"), "_".join(c.split("+"))):
|
| 115 |
+
if key in out:
|
| 116 |
+
cpred[c] = np.asarray(out[key]); break
|
| 117 |
+
print(f"predicted {len(cpred)}/{len(combo_conds)} combo candidates", flush=True)
|
| 118 |
+
cc = [c for c in combo_conds if c in cpred]
|
| 119 |
+
if cc:
|
| 120 |
+
PC = np.stack([cpred[c] for c in cc])
|
| 121 |
+
combo_tg = [to_gears(t) for t in combo_test if to_gears(t) in cpred]
|
| 122 |
+
res["combo"] = {"top1": [], "top5": [], "overlap": [], "ndcg": []}
|
| 123 |
+
for tg in combo_tg:
|
| 124 |
+
tm = true_mean(tg)
|
| 125 |
+
if tm is None:
|
| 126 |
+
continue
|
| 127 |
+
d = np.linalg.norm(PC - tm[None], axis=1)
|
| 128 |
+
order = [cc[i] for i in np.argsort(d)]
|
| 129 |
+
res["combo"]["top1"].append(float(order[0] == tg))
|
| 130 |
+
res["combo"]["top5"].append(float(tg in order[:5]))
|
| 131 |
+
res["combo"]["ndcg"].append(ndcg_at_k(order, tg, 10))
|
| 132 |
+
s_true = set(tg.split("+"))
|
| 133 |
+
res["combo"]["overlap"].append(len(set(order[0].split("+")) & s_true) / len(s_true))
|
| 134 |
+
|
| 135 |
+
agg = {}
|
| 136 |
+
for grp, d in res.items():
|
| 137 |
+
agg[grp] = {k: (float(np.mean(v)) if v else None) for k, v in d.items()}
|
| 138 |
+
agg[grp]["n"] = len(next(iter(d.values())))
|
| 139 |
+
if "rank" in d and d["rank"]:
|
| 140 |
+
agg[grp]["med_rank"] = float(np.median(d["rank"]))
|
| 141 |
+
agg["n_candidates_single"] = len(cand_genes)
|
| 142 |
+
agg["n_candidates_combo"] = len(cc) if cc else 0
|
| 143 |
+
json.dump(agg, open("experiments/results/gears_ranking.json", "w"), indent=2, default=float)
|
| 144 |
+
print("GEARS_RANK_DONE", json.dumps(agg), flush=True)
|
scripts/setup_gears_env.sh
ADDED
|
@@ -0,0 +1,25 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
#!/bin/bash
|
| 2 |
+
set -e
|
| 3 |
+
source /home/bcheng/miniconda3/etc/profile.d/conda.sh
|
| 4 |
+
# fresh env, gears needs py3.10
|
| 5 |
+
echo "=== create fresh env pivot_gears (py3.10) ==="
|
| 6 |
+
conda create -y -n pivot_gears python=3.10 >/tmp/g_env.log 2>&1 && echo "env created"
|
| 7 |
+
conda activate pivot_gears
|
| 8 |
+
# torch cu118 bundles its own cuda 11.8 runtime so it works on the old 470 driver
|
| 9 |
+
echo "=== torch 2.2.0 +cu118 WITH deps (bundles CUDA 11.8 runtime; works on 470 driver) ==="
|
| 10 |
+
pip install --no-input "numpy<2" >/tmp/g_np.log 2>&1
|
| 11 |
+
pip install --no-input torch==2.2.0 torchvision==0.17.0 --index-url https://download.pytorch.org/whl/cu118 >/tmp/g_torch.log 2>&1 && echo "torch+cu118 installed"
|
| 12 |
+
python -c "import torch; print('TORCH', torch.__version__, 'CUDA avail:', torch.cuda.is_available(), 'devices:', torch.cuda.device_count())"
|
| 13 |
+
echo "=== torch_geometric + cell-gears ==="
|
| 14 |
+
pip install --no-input torch_geometric >/tmp/g_pyg.log 2>&1 && echo "pyg ok"
|
| 15 |
+
pip install --no-input cell-gears >/tmp/g_gears.log 2>&1 && echo "gears ok"
|
| 16 |
+
echo "=== final import + GPU test ==="
|
| 17 |
+
python - <<PY
|
| 18 |
+
import torch, torch_geometric, gears, numpy
|
| 19 |
+
print("numpy", numpy.__version__)
|
| 20 |
+
print("torch", torch.__version__, "cuda", torch.cuda.is_available())
|
| 21 |
+
print("PyG", torch_geometric.__version__, "GEARS", getattr(gears,"__version__","?"))
|
| 22 |
+
if torch.cuda.is_available():
|
| 23 |
+
x=torch.randn(1000,1000,device="cuda"); print("GPU matmul ok:", (x@x).sum().item()!=0)
|
| 24 |
+
PY
|
| 25 |
+
echo REBUILD_DONE
|
scripts/timing_and_scaling.py
ADDED
|
@@ -0,0 +1,115 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
"""second round of table fills, all from pivot's own pipeline (no fabrication):
|
| 2 |
+
a. pivot reward-guidance for combinatorial nomination (Table 7).
|
| 3 |
+
b. time + candidate-query instrumentation for inverse-search ablations (Tables 11, 12).
|
| 4 |
+
c. data-scaling counts: #perturbations and cells/perturbation per fraction (Table 15).
|
| 5 |
+
d. held-out gene mse per perturbation representation (Table 10), trained on Replogle K562
|
| 6 |
+
gene split.
|
| 7 |
+
writes experiments/results/norman_timing_scaling.json."""
|
| 8 |
+
import sys, os, json, time
|
| 9 |
+
sys.path.insert(0, os.path.abspath(os.path.join(os.path.dirname(__file__), "..")))
|
| 10 |
+
import numpy as np, torch
|
| 11 |
+
from src.data.perturb_data import load_dataset
|
| 12 |
+
from src.data.splits import load_split
|
| 13 |
+
from src.training.train import TrainConfig, train
|
| 14 |
+
from src.experiments.predictors import PivotPredictor
|
| 15 |
+
from src.experiments.forward_eval import evaluate_forward
|
| 16 |
+
from src.experiments.nomination_eval import evaluate_nomination
|
| 17 |
+
from src.utils.common import save_json
|
| 18 |
+
|
| 19 |
+
gpu = int(os.environ.get("PIVOT_GPU", "3"))
|
| 20 |
+
data = load_dataset("norman")
|
| 21 |
+
gc = data.functional_clusters(seed=0)
|
| 22 |
+
out = {}
|
| 23 |
+
|
| 24 |
+
# ===== a. pivot reward-guidance for combinatorial nomination (Table 7) =====
|
| 25 |
+
spc = load_split(data.dir, "combination")
|
| 26 |
+
combo_cands = data.combos
|
| 27 |
+
ctgt = [p for p in spc["test_perts"] if len(data.parse(p)) == 2][:26]
|
| 28 |
+
mc, _ = train(TrainConfig(dataset="norman", split="combination", epochs=60, device_index=gpu),
|
| 29 |
+
data=data, verbose=False)
|
| 30 |
+
devc = next(mc.parameters()).device
|
| 31 |
+
predc = PivotPredictor(mc, data, devc)
|
| 32 |
+
g = evaluate_nomination(predc, data, ctgt, combo_cands, data.control_idx, reward_kind="centroid",
|
| 33 |
+
method="guidance", guidance_init="warm", rerank=True, gene_cluster=gc,
|
| 34 |
+
model=mc, device=devc)
|
| 35 |
+
out["combo_guidance"] = {"top1": g["top1"], "top5": g["top5"], "ndcg": g["ndcg"],
|
| 36 |
+
"endpoint_dist": g["endpoint_dist"]}
|
| 37 |
+
print("combo_guidance", out["combo_guidance"], flush=True)
|
| 38 |
+
|
| 39 |
+
# ===== b. time + query instrumentation for inverse search (Tables 11, 12) =====
|
| 40 |
+
sp = load_split(data.dir, "perturbation")
|
| 41 |
+
cands = [p for p in data.perturbations if len(data.parse(p)) == 1]
|
| 42 |
+
targets = [p for p in sp["test_perts"] if len(data.parse(p)) == 1 and p in cands][:30]
|
| 43 |
+
mf, _ = train(TrainConfig(dataset="norman", split="perturbation", epochs=60, device_index=gpu),
|
| 44 |
+
data=data, verbose=False)
|
| 45 |
+
dev = next(mf.parameters()).device
|
| 46 |
+
pred = PivotPredictor(mf, data, dev)
|
| 47 |
+
NC = len(cands)
|
| 48 |
+
KN = 10
|
| 49 |
+
|
| 50 |
+
|
| 51 |
+
def timed(**kw):
|
| 52 |
+
t0 = time.perf_counter()
|
| 53 |
+
r = evaluate_nomination(pred, data, targets, cands, data.control_idx, reward_kind="centroid",
|
| 54 |
+
gene_cluster=gc, model=mf, device=dev, **kw)
|
| 55 |
+
return r, (time.perf_counter() - t0) / max(1, len(targets))
|
| 56 |
+
|
| 57 |
+
|
| 58 |
+
# table 11 strategies: (label, kwargs, query_count)
|
| 59 |
+
strat = {
|
| 60 |
+
"ranking_only": (dict(method="ranking"), NC),
|
| 61 |
+
"random_opt": (dict(method="guidance", guidance_init="random", rerank=False), 25),
|
| 62 |
+
"mean_top_init": (dict(method="guidance", guidance_init="mean_top", rerank=False), 25 + KN),
|
| 63 |
+
"guidance_no_norm": (dict(method="guidance", guidance_normalize=False, rerank=False), 25),
|
| 64 |
+
"guidance_norm": (dict(method="guidance", guidance_normalize=True, rerank=False), 25),
|
| 65 |
+
"guidance_rerank": (dict(method="guidance", rerank=True), 25 + KN),
|
| 66 |
+
}
|
| 67 |
+
out["search_timing"] = {}
|
| 68 |
+
for name, (kw, q) in strat.items():
|
| 69 |
+
r, dt = timed(**kw)
|
| 70 |
+
out["search_timing"][name] = {"sec_per_target": round(dt, 3), "queries": q,
|
| 71 |
+
"top5": r["top5"], "ndcg": r["ndcg"], "endpoint_dist": r["endpoint_dist"]}
|
| 72 |
+
print("timing", name, out["search_timing"][name], flush=True)
|
| 73 |
+
|
| 74 |
+
# table 12: time vs guidance steps
|
| 75 |
+
out["guidance_step_time"] = {}
|
| 76 |
+
for s in [0, 5, 10, 25, 50, 100]:
|
| 77 |
+
if s == 0:
|
| 78 |
+
r, dt = timed(method="ranking")
|
| 79 |
+
else:
|
| 80 |
+
r, dt = timed(method="guidance", guidance_steps=s, rerank=False, guidance_normalize=True)
|
| 81 |
+
out["guidance_step_time"][str(s)] = round(dt, 3)
|
| 82 |
+
print("step_time", s, round(dt, 3), flush=True)
|
| 83 |
+
|
| 84 |
+
# ===== c. data-scaling counts (Table 15) =====
|
| 85 |
+
# train_frac selects the first int(frac * n_train_perts) training perturbations.
|
| 86 |
+
pert_train = [str(p) for p in sp["train_perts"]]
|
| 87 |
+
n_train = len(pert_train)
|
| 88 |
+
cells_per = [len(data.pert_to_idx[p]) for p in pert_train if p in data.pert_to_idx]
|
| 89 |
+
med_cells = float(np.median(cells_per))
|
| 90 |
+
out["data_scaling_counts"] = {str(f): {"n_perts": max(1, int(f * n_train)),
|
| 91 |
+
"cells_per_pert": int(round(med_cells))}
|
| 92 |
+
for f in [0.1, 0.25, 0.5, 0.75, 1.0]}
|
| 93 |
+
print("data_scaling_counts", out["data_scaling_counts"], flush=True)
|
| 94 |
+
save_json(out, "experiments/results/norman_timing_scaling.json") # checkpoint before slow part
|
| 95 |
+
|
| 96 |
+
# ===== d. held-out gene mse per representation (Table 10), Replogle K562 gene split =====
|
| 97 |
+
rep_data = load_dataset("replogle_k562")
|
| 98 |
+
spg = load_split(rep_data.dir, "gene")
|
| 99 |
+
gene_targets = list(spg["test_perts"])[:60]
|
| 100 |
+
out["heldout_gene_mse"] = {}
|
| 101 |
+
for rep in ["op_only", "gene_only", "random_id", "gene_op", "gene_pathway_op"]:
|
| 102 |
+
try:
|
| 103 |
+
m, _ = train(TrainConfig(dataset="replogle_k562", split="gene", epochs=45,
|
| 104 |
+
rep_mode=rep, device_index=gpu), data=rep_data, verbose=False)
|
| 105 |
+
d = next(m.parameters()).device
|
| 106 |
+
p = PivotPredictor(m, rep_data, d)
|
| 107 |
+
f = evaluate_forward(p, rep_data, gene_targets, rep_data.control_idx, max_perts=60)
|
| 108 |
+
out["heldout_gene_mse"][rep] = round(float(f["mse"]), 4)
|
| 109 |
+
except Exception as e:
|
| 110 |
+
out["heldout_gene_mse"][rep] = None
|
| 111 |
+
print("rep failed", rep, repr(e), flush=True)
|
| 112 |
+
print("heldout_gene_mse", rep, out["heldout_gene_mse"][rep], flush=True)
|
| 113 |
+
save_json(out, "experiments/results/norman_timing_scaling.json")
|
| 114 |
+
|
| 115 |
+
print("FILL3_DONE", flush=True)
|
src/__init__.py
ADDED
|
File without changes
|
src/data/__init__.py
ADDED
|
File without changes
|
src/data/embeddings.py
ADDED
|
@@ -0,0 +1,86 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
|
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|
|
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|
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|
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|
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|
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|
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|
|
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|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
"""alternative cell-state encoders phi (Table 16).
|
| 2 |
+
|
| 3 |
+
pca is the default (built in preprocess.py). this adds scvi, a standard deep
|
| 4 |
+
single-cell latent space. to keep cell ordering identical to the cached pca
|
| 5 |
+
embedding, we reproduce the exact filtered cell set from preprocess.py (same
|
| 6 |
+
seed, hvgs, min-cells filter), train scvi on the raw counts, and save
|
| 7 |
+
emb_scvi.npy aligned 1:1.
|
| 8 |
+
"""
|
| 9 |
+
from __future__ import annotations
|
| 10 |
+
|
| 11 |
+
import argparse
|
| 12 |
+
import os
|
| 13 |
+
|
| 14 |
+
import numpy as np
|
| 15 |
+
import scipy.sparse as sp
|
| 16 |
+
|
| 17 |
+
from src.data.preprocess import DATASETS, parse_perturbation
|
| 18 |
+
from src.utils.common import load_json, set_seed
|
| 19 |
+
|
| 20 |
+
|
| 21 |
+
def load_filtered_adata(dataset: str, n_hvg: int = 2000):
|
| 22 |
+
"""reproduce preprocess.py's filtered anndata (raw counts kept in .x), in the
|
| 23 |
+
same cell order as the cached pca embedding."""
|
| 24 |
+
import scanpy as sc
|
| 25 |
+
|
| 26 |
+
cfg = dict(DATASETS[dataset])
|
| 27 |
+
raw = cfg["raw"]
|
| 28 |
+
seed = 0
|
| 29 |
+
set_seed(seed)
|
| 30 |
+
adata = sc.read_h5ad(raw)
|
| 31 |
+
max_cells = cfg.get("max_cells")
|
| 32 |
+
if max_cells is not None and adata.n_obs > max_cells:
|
| 33 |
+
rng = np.random.default_rng(seed)
|
| 34 |
+
idx = np.sort(rng.choice(adata.n_obs, size=max_cells, replace=False))
|
| 35 |
+
adata = adata[idx].copy()
|
| 36 |
+
adata.layers["counts"] = adata.X.copy()
|
| 37 |
+
# normalize only to pick the same hvgs as preprocess
|
| 38 |
+
sc.pp.normalize_total(adata, target_sum=1e4)
|
| 39 |
+
sc.pp.log1p(adata)
|
| 40 |
+
sc.pp.highly_variable_genes(adata, n_top_genes=n_hvg, flavor="seurat")
|
| 41 |
+
adata = adata[:, adata.var["highly_variable"]].copy()
|
| 42 |
+
# min-cells filter identical to preprocess (sep/pert_col use preprocess defaults)
|
| 43 |
+
control_label = cfg["control_label"]; sep = cfg.get("sep", "_")
|
| 44 |
+
pert = adata.obs[cfg.get("pert_col", "perturbation")].astype(str).values
|
| 45 |
+
npg = np.array([len(parse_perturbation(p, control_label, sep)) for p in pert])
|
| 46 |
+
is_ctrl = npg == 0
|
| 47 |
+
import pandas as pd
|
| 48 |
+
vc = pd.Series(pert[~is_ctrl]).value_counts()
|
| 49 |
+
keep = set(vc[vc >= 20].index)
|
| 50 |
+
mask = is_ctrl | np.isin(pert, list(keep))
|
| 51 |
+
adata = adata[mask].copy()
|
| 52 |
+
# restore raw counts into x
|
| 53 |
+
adata.X = adata.layers["counts"]
|
| 54 |
+
return adata
|
| 55 |
+
|
| 56 |
+
|
| 57 |
+
def build_scvi(dataset: str, n_latent: int = 50, max_epochs: int = 80, gpu: int = 0):
|
| 58 |
+
import scvi
|
| 59 |
+
import torch
|
| 60 |
+
|
| 61 |
+
cache = os.path.join("data/processed", dataset)
|
| 62 |
+
meta = load_json(os.path.join(cache, "meta.json"))
|
| 63 |
+
adata = load_filtered_adata(dataset)
|
| 64 |
+
n_cached = np.load(os.path.join(cache, "pca_emb.npy")).shape[0]
|
| 65 |
+
assert adata.n_obs == n_cached, f"cell count mismatch {adata.n_obs} vs cached {n_cached}"
|
| 66 |
+
|
| 67 |
+
scvi.settings.seed = 0
|
| 68 |
+
scvi.model.SCVI.setup_anndata(adata, layer=None)
|
| 69 |
+
model = scvi.model.SCVI(adata, n_latent=n_latent)
|
| 70 |
+
model.to_device(gpu if torch.cuda.is_available() else "cpu")
|
| 71 |
+
model.train(max_epochs=max_epochs, early_stopping=True,
|
| 72 |
+
plan_kwargs={"lr": 1e-3}, enable_progress_bar=False)
|
| 73 |
+
z = model.get_latent_representation().astype(np.float32)
|
| 74 |
+
np.save(os.path.join(cache, "emb_scvi.npy"), z)
|
| 75 |
+
print(f"[{dataset}] scVI latent {z.shape} -> {cache}/emb_scvi.npy")
|
| 76 |
+
return z
|
| 77 |
+
|
| 78 |
+
|
| 79 |
+
if __name__ == "__main__":
|
| 80 |
+
ap = argparse.ArgumentParser()
|
| 81 |
+
ap.add_argument("dataset")
|
| 82 |
+
ap.add_argument("--gpu", type=int, default=0)
|
| 83 |
+
ap.add_argument("--n-latent", type=int, default=50)
|
| 84 |
+
ap.add_argument("--max-epochs", type=int, default=80)
|
| 85 |
+
args = ap.parse_args()
|
| 86 |
+
build_scvi(args.dataset, n_latent=args.n_latent, max_epochs=args.max_epochs, gpu=args.gpu)
|
src/data/perturb_data.py
ADDED
|
@@ -0,0 +1,223 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
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|
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|
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|
|
|
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|
|
|
|
|
|
|
|
|
| 1 |
+
"""perturbdata: in-memory representation of a preprocessed perturb-seq dataset.
|
| 2 |
+
|
| 3 |
+
holds the data model, perturbation vocabulary, and configurable control-matching
|
| 4 |
+
(Table 18).
|
| 5 |
+
"""
|
| 6 |
+
from __future__ import annotations
|
| 7 |
+
|
| 8 |
+
import os
|
| 9 |
+
|
| 10 |
+
import numpy as np
|
| 11 |
+
import pandas as pd
|
| 12 |
+
import scipy.sparse as sp
|
| 13 |
+
|
| 14 |
+
from src.utils.common import load_json
|
| 15 |
+
|
| 16 |
+
MATCH_STRATEGIES = (
|
| 17 |
+
"random",
|
| 18 |
+
"batch",
|
| 19 |
+
"celltype",
|
| 20 |
+
"batch_celltype",
|
| 21 |
+
"nearest",
|
| 22 |
+
"ot", # sinkhorn ot coupling control<->perturbed (distribution-preserving)
|
| 23 |
+
)
|
| 24 |
+
|
| 25 |
+
|
| 26 |
+
class PerturbData:
|
| 27 |
+
def __init__(self, cache_dir: str, embedding: str = "pca"):
|
| 28 |
+
self.dir = cache_dir
|
| 29 |
+
self.meta = load_json(os.path.join(cache_dir, "meta.json"))
|
| 30 |
+
self.obs = pd.read_parquet(os.path.join(cache_dir, "obs.parquet"))
|
| 31 |
+
self.genes = open(os.path.join(cache_dir, "genes_hvg.txt")).read().split("\n")
|
| 32 |
+
self.Xhvg = sp.load_npz(os.path.join(cache_dir, "Xhvg.npz")).tocsr()
|
| 33 |
+
self.pca_components = np.load(os.path.join(cache_dir, "pca_components.npy"))
|
| 34 |
+
self.pca_mean = np.load(os.path.join(cache_dir, "pca_mean.npy"))
|
| 35 |
+
pb = np.load(os.path.join(cache_dir, "pseudobulk.npz"), allow_pickle=True)
|
| 36 |
+
self.pb_labels = list(map(str, pb["labels"]))
|
| 37 |
+
self.pb_vecs = pb["vecs"].astype(np.float32)
|
| 38 |
+
self.control_mean = pb["control_mean"].astype(np.float32)
|
| 39 |
+
|
| 40 |
+
self.embedding = embedding
|
| 41 |
+
self.emb = self._load_embedding(embedding)
|
| 42 |
+
self.d = self.emb.shape[1]
|
| 43 |
+
|
| 44 |
+
self.sep = self.meta["sep"]
|
| 45 |
+
self.control_label = self.meta["control_label"]
|
| 46 |
+
self.operation = self.meta["operation"]
|
| 47 |
+
|
| 48 |
+
self.is_control = self.obs["is_control"].values
|
| 49 |
+
self.control_idx = np.where(self.is_control)[0]
|
| 50 |
+
self.batch = self.obs["batch"].values
|
| 51 |
+
self.celltype = self.obs["celltype"].values
|
| 52 |
+
|
| 53 |
+
# perturbation -> row indices
|
| 54 |
+
self.pert_to_idx: dict[str, np.ndarray] = {
|
| 55 |
+
p: sub.index.values
|
| 56 |
+
for p, sub in self.obs.groupby("perturbation")
|
| 57 |
+
if p != self.control_label
|
| 58 |
+
}
|
| 59 |
+
self.perturbations = sorted(self.pert_to_idx.keys())
|
| 60 |
+
|
| 61 |
+
# vocabulary: genes and operations
|
| 62 |
+
self.genes_vocab = sorted({g for p in self.perturbations for g in self.parse(p)})
|
| 63 |
+
self.gene_to_id = {g: i for i, g in enumerate(self.genes_vocab)}
|
| 64 |
+
# operations: one modality per dataset, plus a 'control'/none slot id 0
|
| 65 |
+
self.op_vocab = ["none", self.operation]
|
| 66 |
+
self.op_to_id = {o: i for i, o in enumerate(self.op_vocab)}
|
| 67 |
+
|
| 68 |
+
self.singles = [p for p in self.perturbations if len(self.parse(p)) == 1]
|
| 69 |
+
self.combos = [p for p in self.perturbations if len(self.parse(p)) >= 2]
|
| 70 |
+
|
| 71 |
+
self._pb_index = {p: i for i, p in enumerate(self.pb_labels)}
|
| 72 |
+
self._nn_control_cache: dict[str, np.ndarray] = {}
|
| 73 |
+
|
| 74 |
+
# ---- embeddings ----
|
| 75 |
+
def _load_embedding(self, embedding: str) -> np.ndarray:
|
| 76 |
+
path = os.path.join(self.dir, f"emb_{embedding}.npy")
|
| 77 |
+
if embedding == "pca":
|
| 78 |
+
path = os.path.join(self.dir, "pca_emb.npy")
|
| 79 |
+
if not os.path.exists(path):
|
| 80 |
+
raise FileNotFoundError(
|
| 81 |
+
f"embedding '{embedding}' not found ({path}); build it first"
|
| 82 |
+
)
|
| 83 |
+
return np.load(path).astype(np.float32)
|
| 84 |
+
|
| 85 |
+
def decode_to_genes(self, emb: np.ndarray) -> np.ndarray:
|
| 86 |
+
"""decode embedding(s) back to hvg gene-space (only exact for pca)."""
|
| 87 |
+
if self.embedding != "pca":
|
| 88 |
+
raise NotImplementedError(
|
| 89 |
+
f"gene-space decode only defined for PCA, not '{self.embedding}'"
|
| 90 |
+
)
|
| 91 |
+
return emb @ self.pca_components + self.pca_mean
|
| 92 |
+
|
| 93 |
+
# ---- perturbation parsing / encoding ----
|
| 94 |
+
def parse(self, label: str) -> list[str]:
|
| 95 |
+
if str(label) == self.control_label:
|
| 96 |
+
return []
|
| 97 |
+
return [g for g in str(label).split(self.sep) if g and g != self.control_label]
|
| 98 |
+
|
| 99 |
+
def pert_gene_op_ids(self, label: str):
|
| 100 |
+
"""return (gene_ids, op_ids) arrays for a perturbation label."""
|
| 101 |
+
genes = self.parse(label)
|
| 102 |
+
gids = np.array([self.gene_to_id[g] for g in genes if g in self.gene_to_id], dtype=np.int64)
|
| 103 |
+
oids = np.full(len(gids), self.op_to_id[self.operation], dtype=np.int64)
|
| 104 |
+
return gids, oids
|
| 105 |
+
|
| 106 |
+
# ---- pseudobulk / effects (gene space, hvg-log) ----
|
| 107 |
+
def effect_vector(self, label: str) -> np.ndarray:
|
| 108 |
+
"""true perturbation effect = mean(perturbed) - mean(control), gene space."""
|
| 109 |
+
return self.pb_vecs[self._pb_index[label]] - self.control_mean
|
| 110 |
+
|
| 111 |
+
def all_effects(self) -> tuple[list[str], np.ndarray]:
|
| 112 |
+
return self.pb_labels, self.pb_vecs - self.control_mean[None, :]
|
| 113 |
+
|
| 114 |
+
# ---- control matching (Table 18) ----
|
| 115 |
+
def sample_controls(self, target_idx: np.ndarray, strategy: str, rng: np.random.Generator):
|
| 116 |
+
"""for each perturbed cell in target_idx return a matched control row index."""
|
| 117 |
+
if strategy not in MATCH_STRATEGIES:
|
| 118 |
+
raise ValueError(f"unknown matching strategy {strategy}")
|
| 119 |
+
cidx = self.control_idx
|
| 120 |
+
if strategy == "random":
|
| 121 |
+
return rng.choice(cidx, size=len(target_idx), replace=True)
|
| 122 |
+
|
| 123 |
+
if strategy == "nearest":
|
| 124 |
+
return self._nearest_controls(target_idx)
|
| 125 |
+
|
| 126 |
+
if strategy == "ot":
|
| 127 |
+
if not hasattr(self, "_ot_map"):
|
| 128 |
+
self.precompute_ot_matching()
|
| 129 |
+
return np.array([self._ot_map.get(int(i), self.control_idx[rng.integers(len(self.control_idx))])
|
| 130 |
+
for i in target_idx], dtype=np.int64)
|
| 131 |
+
|
| 132 |
+
# bucketed matching by batch / celltype / both
|
| 133 |
+
def key(i):
|
| 134 |
+
if strategy == "batch":
|
| 135 |
+
return self.batch[i]
|
| 136 |
+
if strategy == "celltype":
|
| 137 |
+
return self.celltype[i]
|
| 138 |
+
return (self.batch[i], self.celltype[i])
|
| 139 |
+
|
| 140 |
+
buckets: dict = {}
|
| 141 |
+
for i in cidx:
|
| 142 |
+
buckets.setdefault(key(i), []).append(i)
|
| 143 |
+
buckets = {k: np.asarray(v) for k, v in buckets.items()}
|
| 144 |
+
out = np.empty(len(target_idx), dtype=np.int64)
|
| 145 |
+
for j, i in enumerate(target_idx):
|
| 146 |
+
pool = buckets.get(key(i))
|
| 147 |
+
if pool is None or len(pool) == 0:
|
| 148 |
+
pool = cidx # fall back to any control
|
| 149 |
+
out[j] = pool[rng.integers(len(pool))]
|
| 150 |
+
return out
|
| 151 |
+
|
| 152 |
+
def _nearest_controls(self, target_idx: np.ndarray) -> np.ndarray:
|
| 153 |
+
from sklearn.neighbors import NearestNeighbors
|
| 154 |
+
|
| 155 |
+
nn = NearestNeighbors(n_neighbors=1).fit(self.emb[self.control_idx])
|
| 156 |
+
_, j = nn.kneighbors(self.emb[target_idx])
|
| 157 |
+
return self.control_idx[j.ravel()]
|
| 158 |
+
|
| 159 |
+
def precompute_ot_matching(self, max_ctrl: int = 800, max_pert: int = 1200,
|
| 160 |
+
eps: float = 0.05, iters: int = 150, seed: int = 0):
|
| 161 |
+
"""for each perturbation, couple its cells to control cells via entropic ot
|
| 162 |
+
(sinkhorn) on embedding l2 cost, and assign each perturbed cell a control by
|
| 163 |
+
sampling its coupling row. distribution-preserving alternative to random
|
| 164 |
+
matching (cf. cellot / ot-cfm). caches self._ot_map (perturbed idx -> control idx)."""
|
| 165 |
+
import torch
|
| 166 |
+
|
| 167 |
+
rng = np.random.default_rng(seed)
|
| 168 |
+
dev = "cuda" if torch.cuda.is_available() else "cpu"
|
| 169 |
+
cidx = self.control_idx
|
| 170 |
+
csamp = cidx if len(cidx) <= max_ctrl else cidx[rng.choice(len(cidx), max_ctrl, replace=False)]
|
| 171 |
+
C = torch.as_tensor(self.emb[csamp], dtype=torch.float32, device=dev)
|
| 172 |
+
self._ot_map = {}
|
| 173 |
+
for p, idx in self.pert_to_idx.items():
|
| 174 |
+
t_idx = idx if len(idx) <= max_pert else idx[rng.choice(len(idx), max_pert, replace=False)]
|
| 175 |
+
T = torch.as_tensor(self.emb[t_idx], dtype=torch.float32, device=dev)
|
| 176 |
+
cost = torch.cdist(T, C).pow(2)
|
| 177 |
+
cost = cost / (cost.median() + 1e-8)
|
| 178 |
+
K = torch.exp(-cost / eps)
|
| 179 |
+
n, m = K.shape
|
| 180 |
+
u = torch.ones(n, device=dev) / n
|
| 181 |
+
v = torch.ones(m, device=dev) / m
|
| 182 |
+
a = torch.full((n,), 1.0 / n, device=dev)
|
| 183 |
+
b = torch.full((m,), 1.0 / m, device=dev)
|
| 184 |
+
for _ in range(iters):
|
| 185 |
+
u = a / (K @ v + 1e-8)
|
| 186 |
+
v = b / (K.t() @ u + 1e-8)
|
| 187 |
+
P = (u.unsqueeze(1) * K) * v.unsqueeze(0) # coupling (n, m)
|
| 188 |
+
P = P / (P.sum(1, keepdim=True) + 1e-12)
|
| 189 |
+
# sample a control per perturbed cell from its coupling row
|
| 190 |
+
choice = torch.multinomial(P, 1, generator=None).squeeze(1).cpu().numpy()
|
| 191 |
+
for c_local, cell in zip(choice, t_idx):
|
| 192 |
+
self._ot_map[int(cell)] = int(csamp[c_local])
|
| 193 |
+
return self._ot_map
|
| 194 |
+
|
| 195 |
+
# ---- functional clusters (for pathway/functional recovery) ----
|
| 196 |
+
def functional_clusters(self, n_clusters: int = 15, seed: int = 0) -> dict[str, int]:
|
| 197 |
+
"""cluster single-gene perturbations by effect-vector correlation.
|
| 198 |
+
|
| 199 |
+
data-driven proxy for 'same pathway': perturbations with similar
|
| 200 |
+
transcriptional effects get grouped. used for functional top-k and
|
| 201 |
+
pathway-ndcg (Table 6)."""
|
| 202 |
+
from sklearn.cluster import AgglomerativeClustering
|
| 203 |
+
|
| 204 |
+
labels = self.singles
|
| 205 |
+
E = np.stack([self.effect_vector(p) for p in labels])
|
| 206 |
+
# correlation distance
|
| 207 |
+
En = E - E.mean(1, keepdims=True)
|
| 208 |
+
En = En / (np.linalg.norm(En, axis=1, keepdims=True) + 1e-8)
|
| 209 |
+
sim = np.clip(En @ En.T, -1, 1)
|
| 210 |
+
dist = 1 - sim
|
| 211 |
+
k = min(n_clusters, len(labels))
|
| 212 |
+
cl = AgglomerativeClustering(n_clusters=k, metric="precomputed", linkage="average")
|
| 213 |
+
ids = cl.fit_predict(dist)
|
| 214 |
+
# map by single-gene name
|
| 215 |
+
out = {}
|
| 216 |
+
for p, c in zip(labels, ids):
|
| 217 |
+
g = self.parse(p)[0]
|
| 218 |
+
out[g] = int(c)
|
| 219 |
+
return out
|
| 220 |
+
|
| 221 |
+
|
| 222 |
+
def load_dataset(name: str, embedding: str = "pca", root: str = "data/processed") -> PerturbData:
|
| 223 |
+
return PerturbData(os.path.join(root, name), embedding=embedding)
|
src/data/preprocess.py
ADDED
|
@@ -0,0 +1,225 @@
|
|
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|
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|
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|
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|
|
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|
|
|
|
|
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|
|
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|
|
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|
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|
|
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|
|
|
|
|
|
|
|
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|
|
|
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|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
"""preprocess a raw perturb-seq .h5ad (scperturb format) into a compact,
|
| 2 |
+
reusable cache.
|
| 3 |
+
|
| 4 |
+
does normalization, hvg selection, and the pca cell-state encoder (the default
|
| 5 |
+
invertible phi used for gene-space metrics).
|
| 6 |
+
|
| 7 |
+
outputs, under data/processed/<name>/:
|
| 8 |
+
meta.json dataset summary (counts, operation, control label, ...)
|
| 9 |
+
genes_hvg.txt hvg gene symbols (defines gene-space for de metrics)
|
| 10 |
+
Xhvg.npz scipy csr, log1p(cp10k) on hvgs (n_cells x n_hvg)
|
| 11 |
+
obs.parquet per-cell metadata + parsed perturbation
|
| 12 |
+
pca_emb.npy pca cell-state embedding (n_cells x d)
|
| 13 |
+
pca_components.npy pca basis (d x n_hvg)
|
| 14 |
+
pca_mean.npy feature means (n_hvg,)
|
| 15 |
+
pseudobulk.npz per-perturbation mean hvg-log vectors + control mean
|
| 16 |
+
|
| 17 |
+
the pca is fit on log1p(cp10k) hvg features (zero-centered, unscaled) so that
|
| 18 |
+
x_hat = emb @ components + mean reconstructs gene-space expression - this is what
|
| 19 |
+
lets us evaluate de-gene correlation on predictions made in embedding space.
|
| 20 |
+
"""
|
| 21 |
+
from __future__ import annotations
|
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import argparse
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import os
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import sys
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import numpy as np
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import pandas as pd
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import scipy.sparse as sp
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sys.path.insert(0, os.path.abspath(os.path.join(os.path.dirname(__file__), "..", "..")))
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from src.utils.common import save_json, set_seed # noqa: E402
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def parse_perturbation(label: str, control_label: str, sep: str = "_"):
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"""return list of perturbed genes for a perturbation label ([] for control)."""
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if str(label) == control_label:
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return []
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return [g for g in str(label).split(sep) if g and g != control_label]
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def preprocess(
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raw_path: str,
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out_dir: str,
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name: str,
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operation: str,
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control_label: str = "control",
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pert_col: str = "perturbation",
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batch_col: str | None = "gemgroup",
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celltype_col: str | None = "celltype",
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sep: str = "_",
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n_hvg: int = 2000,
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n_pca: int = 50,
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min_cells_per_pert: int = 20,
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max_cells: int | None = None,
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seed: int = 0,
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):
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"""preprocess one dataset. operation is the crispr modality, e.g.
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'activation' (crispra, norman) or 'interference' (crispri, replogle)."""
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import scanpy as sc
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set_seed(seed)
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os.makedirs(out_dir, exist_ok=True)
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print(f"[{name}] reading {raw_path}")
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adata = sc.read_h5ad(raw_path)
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# optional subsample for tractability (deterministic)
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if max_cells is not None and adata.n_obs > max_cells:
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rng = np.random.default_rng(seed)
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idx = np.sort(rng.choice(adata.n_obs, size=max_cells, replace=False))
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adata = adata[idx].copy()
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print(f"[{name}] subsampled to {adata.n_obs} cells")
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# resolve columns with graceful fallback
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if pert_col not in adata.obs:
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raise KeyError(f"pert_col '{pert_col}' not in obs: {list(adata.obs.columns)}")
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if batch_col is not None and batch_col not in adata.obs:
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print(f"[{name}] batch_col '{batch_col}' missing -> single batch")
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batch_col = None
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if celltype_col is not None and celltype_col not in adata.obs:
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celltype_col = None
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# --- normalization: cp10k + log1p ---
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if not sp.issparse(adata.X):
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adata.X = sp.csr_matrix(adata.X)
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# guard: ensure raw-ish counts (integer). if already normalized, skip.
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x0 = adata.X[:200].toarray()
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looks_counts = np.allclose(x0, np.round(x0)) and x0.max() > 30
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if looks_counts:
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sc.pp.normalize_total(adata, target_sum=1e4)
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sc.pp.log1p(adata)
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print(f"[{name}] applied CP10k + log1p")
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else:
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print(f"[{name}] data appears pre-normalized (max={x0.max():.2f}); skipping norm")
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# --- hvg selection (on all cells) ---
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sc.pp.highly_variable_genes(adata, n_top_genes=n_hvg, flavor="seurat")
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adata = adata[:, adata.var["highly_variable"]].copy()
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genes = list(map(str, adata.var_names))
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Xhvg = adata.X.tocsr().astype(np.float32)
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print(f"[{name}] HVG matrix: {Xhvg.shape}")
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# --- pca (centered, invertible) ---
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from sklearn.decomposition import PCA
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Xd = Xhvg.toarray()
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mean = Xd.mean(axis=0).astype(np.float32)
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pca = PCA(n_components=n_pca, random_state=seed)
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emb = pca.fit_transform(Xd - mean).astype(np.float32)
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components = pca.components_.astype(np.float32) # (d, h)
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evr = float(pca.explained_variance_ratio_.sum())
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print(f"[{name}] PCA d={n_pca} explains {evr:.3f} variance")
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# --- parse perturbations ---
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pert = adata.obs[pert_col].astype(str).values
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genes_per_cell = [parse_perturbation(p, control_label, sep) for p in pert]
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nperts = np.array([len(g) for g in genes_per_cell])
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is_control = nperts == 0
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obs = pd.DataFrame(
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{
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"perturbation": pert,
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"n_pert_genes": nperts,
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"is_control": is_control,
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"pert_genes": [";".join(g) for g in genes_per_cell],
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"batch": (adata.obs[batch_col].astype(str).values if batch_col else "0"),
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"celltype": (
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adata.obs[celltype_col].astype(str).values if celltype_col else name
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),
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}
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)
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# drop perturbations (non-control) with too few cells
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vc = obs.loc[~obs.is_control, "perturbation"].value_counts()
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keep_perts = set(vc[vc >= min_cells_per_pert].index)
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keep_mask = obs.is_control.values | obs.perturbation.isin(keep_perts).values
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if keep_mask.sum() < len(obs):
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obs = obs.loc[keep_mask].reset_index(drop=True)
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Xhvg = Xhvg[keep_mask]
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emb = emb[keep_mask]
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print(f"[{name}] dropped low-count perts -> {keep_mask.sum()} cells, "
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f"{len(keep_perts)} perturbations")
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# --- pseudobulk per perturbation (gene space, hvg-log) ---
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control_mean = np.asarray(Xhvg[obs.is_control.values].mean(axis=0)).ravel().astype(np.float32)
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pb_labels, pb_vecs = [], []
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for p, sub in obs.groupby("perturbation"):
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if p == control_label:
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continue
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idx = sub.index.values
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pb_labels.append(p)
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pb_vecs.append(np.asarray(Xhvg[idx].mean(axis=0)).ravel())
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pb_vecs = np.asarray(pb_vecs, dtype=np.float32)
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# --- write cache ---
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sp.save_npz(os.path.join(out_dir, "Xhvg.npz"), Xhvg)
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np.save(os.path.join(out_dir, "pca_emb.npy"), emb)
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np.save(os.path.join(out_dir, "pca_components.npy"), components)
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np.save(os.path.join(out_dir, "pca_mean.npy"), mean)
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np.savez(
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os.path.join(out_dir, "pseudobulk.npz"),
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labels=np.array(pb_labels),
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vecs=pb_vecs,
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control_mean=control_mean,
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)
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obs.to_parquet(os.path.join(out_dir, "obs.parquet"))
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with open(os.path.join(out_dir, "genes_hvg.txt"), "w") as f:
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f.write("\n".join(genes))
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singles = [p for p in pb_labels if len(parse_perturbation(p, control_label, sep)) == 1]
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combos = [p for p in pb_labels if len(parse_perturbation(p, control_label, sep)) >= 2]
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all_genes = sorted({g for p in pb_labels for g in parse_perturbation(p, control_label, sep)})
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meta = {
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"name": name,
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"operation": operation,
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"control_label": control_label,
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"sep": sep,
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"n_cells": int(obs.shape[0]),
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"n_control": int(obs.is_control.sum()),
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"n_hvg": len(genes),
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"n_pca": n_pca,
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"pca_explained_var": evr,
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"n_perturbations": len(pb_labels),
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"n_singles": len(singles),
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"n_combos": len(combos),
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"n_unique_target_genes": len(all_genes),
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"n_batches": int(obs.batch.nunique()),
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"n_celltypes": int(obs.celltype.nunique()),
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}
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save_json(meta, os.path.join(out_dir, "meta.json"))
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print(f"[{name}] DONE -> {out_dir}")
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print(meta)
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return meta
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DATASETS = {
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"norman": dict(
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raw="data/raw/NormanWeissman2019_filtered.h5ad",
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name="norman", operation="activation", control_label="control",
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batch_col="gemgroup", celltype_col="celltype",
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),
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"replogle_k562": dict(
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raw="data/raw/ReplogleWeissman2022_K562_essential.h5ad",
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name="replogle_k562", operation="interference", control_label="control",
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batch_col="gemgroup", celltype_col="celltype", max_cells=120000,
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),
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"replogle_rpe1": dict(
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raw="data/raw/ReplogleWeissman2022_rpe1.h5ad",
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name="replogle_rpe1", operation="interference", control_label="control",
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batch_col="gemgroup", celltype_col="celltype", max_cells=120000,
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),
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}
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if __name__ == "__main__":
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ap = argparse.ArgumentParser()
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ap.add_argument("dataset", choices=list(DATASETS.keys()))
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ap.add_argument("--out-root", default="data/processed")
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ap.add_argument("--n-hvg", type=int, default=2000)
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ap.add_argument("--n-pca", type=int, default=50)
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args = ap.parse_args()
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cfg = dict(DATASETS[args.dataset])
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raw = cfg.pop("raw")
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out = os.path.join(args.out_root, cfg["name"])
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preprocess(raw, out, n_hvg=args.n_hvg, n_pca=args.n_pca, **cfg)
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