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squidiff: Predicting cellular development and responses to perturbations using a diffusion model

Squidiff is a diffusion model-based generative framework designed to predict transcriptomic changes across diverse cell types in response to a wide range of environmental changes.

Installation

pip install Squidiff

Model Input:

h5ad file with info:

  • Single-cell count matrix
  • Meta data
  • (optional) additional drug compounds

Features

  • Predicting single-cell transcriptomics upon drug treatments
  • Predicting cell differentiation
  • Predicting gene perturbation

Training Squidiff

python train_squidiff.py --logger_path LOGGER_FIRE_NAME --data_path YOUR_ADATASET.h5ad --resume_checkpoint ptNAME --gene_size 500 --output_dim 500

For incorporating drug structure in training, see the example:

python train_squidiff.py --logger_path logger_files/logger_sciplex_random_split_0 --data_path datasets/sci_plex_train_random_split_0.h5ad --resume_checkpoint sciplex_results_random_split_0 --use_drug_structure True --gene_size 200 --output_dim 200 --control_data_path datasets/sci_plex_train_random_split_0_control.h5ad

Sample Squidiff

sampler = sample_squidiff.sampler(
    model_path = 'simu_results/model.pt',
    gene_size = 100,
    output_dim = 100,
    use_drug_structure = False
)

test_adata_scrna = sc.read_h5ad('datasets/sc_simu_test.h5ad')
z_sem_scrna = sampler.model.encoder(torch.tensor(test_adata_scrna.X).to('cuda'))

scrnas_pred = sampler.pred(z_sem_scrna, gene_size = test_adata_scrna.shape[1])

Demo

Please forward to https://github.com/siyuh/Squidiff_reproducibility for data preparation, model usage, and downstream analysis.

How to cite Squidiff

Please cite:

He, S., Zhu, Y., Tavakol, D.N. et al. Squidiff: predicting cellular development and responses to perturbations using a diffusion model. Nat Methods (2025). https://doi.org/10.1038/s41592-025-02877-y
Predicting cellular responses with conditional diffusion models. Nat Methods (2025). https://doi.org/10.1038/s41592-025-02878-x

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