SpliceVI

SpliceVI is a multimodal variational autoencoder that jointly models gene expression and alternative splicing (junction usage / PSI) from single-cell data. It learns a shared low-dimensional latent representation from paired or unpaired measurements across both modalities, enabling clustering, trajectory inference, imputation, and differential expression and splicing analysis.

Ecosystem overview

Three tools form the splicing analysis ecosystem. They share a common intermediate format, SplicingDataset, so you can swap models without reformatting data.

flowchart TD
    A[BAM files per cell] --> B[regtools junction extract]
    B --> C[ATSEmapper]
    C --> D["SplicingDataset.h5ad\ncell_by_junction_matrix\ncell_by_cluster_matrix"]
    D --> E[LeafletFA]
    D --> F[SpliceVI]
    E --> G["Splicing Programs (K factors)\nCell SP activities"]
    F --> H["Joint latent space\nDifferential analysis"]

Tool	Role	Repo	Docs
ATSEmapper	BAM files → SplicingDataset	daklab/ATSEmapper	—
LeafletFA	Beta-Dirichlet factor model for splicing programs	daklab/LeafletFA	docs
SpliceVI	Multimodal VAE (splicing + gene expression)	daklab/SpliceVI	this site

ATSEmapper is the bridge between the bulk-sequencing infrastructure most labs already run and the single-cell-native format both LeafletFA and SpliceVI consume.

Quick install

git clone https://github.com/daklab/SpliceVI.git
cd SpliceVI
pip install -e .

Minimal example

import mudata
from splicevi import SPLICEVI

mdata = mudata.read_h5mu("train_data.h5mu")

SPLICEVI.setup_mudata(
    mdata,
    rna_layer="length_norm",
    batch_key="mouse.id",
)

model = SPLICEVI(mdata, n_latent=30)
model.train(max_epochs=800)

latent = model.get_latent_representation()   # (cells × n_latent) joint latent space
psi    = model.get_normalized_splicing()     # (cells × junctions) imputed PSI values

See SpliceVI model for the full parameter reference and SpliceVI MuData Object for the expected input structure.

Citation

If you use SpliceVI, please cite:

Vaidyanathan S, Isaev K, Zweig A, Knowles DA. Robust Integration of Sparse Single-Cell Alternative Splicing and Gene Expression Data with SpliceVI. bioRxiv 2025. https://doi.org/10.1101/2025.11.26.690853