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TopicVI: Prior Gene Programs Motivated Cell Subtype or State Definition by Topic Modeling

TopicVI is a Python package that implements topic modeling to define cell subtypes or states based on prior gene programs. It uses the variational autoencoder (VAE) framework and non-negative matrix factorization (NMF) to discover topics in single-cell RNA-seq data, allowing for the identification of distinct cell populations and their functional characteristics.

The key idea of TopicVI is to leverage existing biologicaxl knowledge, in the form of prior gene programs, to guide the topic modeling process. By optimal transport algorithm, TopicVI is able to improve the interpretability and biological relevance of the discovered topics.

The built-in prior gene programs include cell markers, cell states, cell functions, and more. These programs can be used to define cell subtypes or states, and to annotate the discovered topics with biological meaning.

Content Source Category
Human / Mouse cell markers CellMarkerDB v2.0 Cell Markers
Cell markers of different Human tissue ScType Cell Markers
Meta-Program of Immune and Malignant cells Gavish el al. Cell States
Tissue Specific Geneset DAVID Database (2024) Cell States
Gene Ontology Items The Gene Ontology Resource (2017) Cell Functions
KEGG Pathways KEGG DB (2021, Human) Cell Functions
Reactome Pathways Reactome DB (2022) Cell Functions
Hallmarks MSigDB HallMark (2020) Cell Functions

For more details, please reefer to our paper.

Installation

by source code:

Notice to the pytorch version and your CUDA version. We highly recommend you should install the correct pytorch version first, then install TopicVI.

git clone https://github.com/gx-cai/topicvi.git
cd topicvi
pip install -e .

by conda to create a new environment:

conda create -n topicvi python=3.11
conda activate topicvi
conda install scvi-tools>=1.2 leidenalg scanpy pandas python-igraph gseapy -c conda-forge -c bioconda
pip install geomloss scikit-misc harmonypy "flax>=0.8"
pip install -e .

Documentation

See Wiki page for more details.

Citation

If you use TopicVI in your research, please cite the following paper:

TopicVI: A Knowledge-guided deep interpretable model for resolving context-specific gene programs Guoxin Cai, Wenyi Zhao, Xunuo Zhu, Yitao Lin, Binbin Zhou, Ji Cao, Qiaojun He, Bo Yang, Xun Gu, Xushen Xiong, Zhan Zhou bioRxiv 2026.04.08.717220; doi: https://doi.org/10.64898/2026.04.08.717220

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Prior Gene Programs Motivated Cell Subtype or State Definition by Topic Modeling

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