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Data and Intermediate Results

This project does not redistribute the scPerturb h5ad files, Geneformer weights, or large path-D caches in Git.

Public Input Datasets

Download the harmonized scPerturb h5ad files and place them under data/:

Dataset Expected local path Use in manuscript Required contents
Frangieh et al. 2021 melanoma/TIL Perturb-CITE-seq data/FrangiehIzar2021_RNA.h5ad Frangieh CCND1 worked example, token coverage, library-size contamination, DESeq2 target raw counts, perturbation labels, sgRNA/replicate metadata, gene symbols and Ensembl IDs
Replogle et al. 2022 K562 essential-scale CRISPRi data/ReplogleWeissman2022_K562_essential.h5ad cross-dataset DESeq2 increment tests, GATA1 state-shift/de-circularization raw counts, perturbation labels, gemgroup/batch metadata, gene symbols and Ensembl IDs

Access: see scPerturb (Peidli et al. 2024) and https://scperturb.org.

Geneformer Assets

The repository expects Geneformer V2-104M to be available locally:

Geneformer/Geneformer-V2-104M/
Geneformer/geneformer/token_dictionary_gc104M.pkl

Geneformer source/weights are third-party assets and are not redistributed here. Install Geneformer separately so the geneformer Python package is importable.

Large Intermediate Files

Large generated artifacts are not intended for Git. They are available on Zenodo at https://doi.org/10.5281/zenodo.20729460, including:

Artifact class Example local path Purpose
path-D caches benchmark_output/pathd_cache/CCND1_cache.npz cached per-cell/per-gene responses enabling NumPy-only resampling and readout tests
DESeq2 outputs benchmark_output/deseq2/*_replogle_deseq2.npz primary target and increment-test outputs
validation outputs benchmark_output/pathd_validation.csv path-D vs official engine validation

The Zenodo bundle restores the cached intermediate files under benchmark_output/ when extracted at the repository root.

The small curated figure-input CSVs — results/data/token_coverage.csv, results/data/CCND1_curve_main.csv, results/data/CCND1_curve_abl.csv — are committed to this repository (not Zenodo), so Figure 3 reproduces from a clean checkout.

Recomputing Instead of Downloading Caches

The full path-D cache generation requires running Geneformer forward passes for WT and KO token sequences. A CUDA GPU is recommended; the worked Frangieh CCND1 path-D cache was generated on a 4 GB NVIDIA GPU by batching/subsampling.

Representative commands:

python scripts/pipeline/cache_pathd.py CCND1 data/FrangiehIzar2021_RNA.h5ad
python scripts/pipeline/validate_pathd.py
python scripts/pipeline/resample_pathd.py CCND1
python scripts/diagnostics/deseq2_groundtruth.py
python scripts/diagnostics/deseq2_replogle.py HSPA9
python scripts/diagnostics/deseq2_replogle.py SUPT6H
python scripts/diagnostics/deseq2_replogle.py CSE1L
python scripts/diagnostics/deseq2_replogle.py DHX15
python scripts/diagnostics/deseq2_replogle.py GATA1

See README_reproduce_figures.md for panel-level figure provenance and reported_numbers_source_table.csv for manuscript-number provenance.