Spotiphy enables single-cell spatial whole transcriptomics via generative modeling

Spotiphy is a Python package for integrating sequencing-based spatial transcriptomics, scRNA-seq data, and high-resolution histological images. Using a probabilistic generative model, Bayesian inference, and advanced image processing, Spotiphy performs three key tasks:

• Deconvolution – Estimate the abundance of each cell type in every spatial capture area.
• Decomposition – Resolve bulk spatial transcriptomics data down to the single-cell level.
• Pseudo single-cell image reconstruction – Generate images with pseudo single-cell resolution, enabling reconstruction of cell neighborhoods.

These outputs enable a wide range of downstream analyses. For further details, see our Nature Methods publication.

📚 Tutorials & Documentation

Currently available tutorial:

• Mouse cortex analysis: Documentation | Google Colab

Full documentation is available at jyyulab.github.io/Spotiphy.

⚙️ Installation

We recommend using a dedicated conda environment:

conda create -n Spotiphy-env python=3.9
conda activate Spotiphy-env

Spotiphy is built based on Pytorch and TensorFlow, which must be installed manually before use.

# macOS with Apple Silicon
conda install -c apple tensorflow-deps -y
pip install tensorflow-macos==2.16.2 tensorflow-metal==1.2.0
pip install torch

# Windows
pip install torch  # Or follow https://pytorch.org/get-started/locally/ to install with CUDA support
pip install tensorflow==2.16.2

After installing the dependencies, Spotiphy itself can be installed in one of the following ways:

• From GitHub: Installs the latest development version directly from the source code.

pip install git+https://github.com/jyyulab/Spotiphy.git

• From PyPI: Installs the stable release from the Python Package Index (recommended for most users).

pip install spotiphy==0.3.0

To test the Installation, try to import Spotiphy in Python.

import spotiphy

❓ FAQ & Support

Frequently asked questions: Spotiphy FAQ.

For further assistance, start a GitHub Discussion or contact the authors:

• Ziqian Zheng - zzheng92@wisc.edu
• Jiyuan Yang - jiyuan.yang@stjude.org

Cite Spotiphy:

@article{yang2025spotiphy,
  title={Spotiphy enables single-cell spatial whole transcriptomics across an entire section},
  author={Yang, Jiyuan and Zheng, Ziqian and Jiao, Yun and Yu, Kaiwen and Bhatara, Sheetal and Yang, Xu and Natarajan, Sivaraman and Zhang, Jiahui and Pan, Qingfei and Easton, John and others},
  journal={Nature Methods},
  pages={1--13},
  year={2025},
  publisher={Nature Publishing Group US New York}
}

Nature Methods article