LeafletFA

LeafletFA is a scalable probabilistic Beta-Dirichlet factor model that decomposes single-cell splicing variation into interpretable Splicing Programs (SPs). It discovers coordinated modules of Alternative Transcript Structure Events (ATSEs) that reflect biological states — cellular aging, lineage, stress — without requiring pre-defined labels.

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
ATSEmapper	BAM files → SplicingDataset	daklab/ATSEmapper
LeafletFA	Beta-Dirichlet factor model	daklab/LeafletFA
SpliceVI	Multimodal VAE (splicing + expression)	daklab/SpliceVI

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/LeafletFA.git
cd LeafletFA
pip install -e .

Minimal example

import anndata as ad
from leafletfa import LeafletFA

adata = ad.read_h5ad("splicing_dataset.h5ad")

model = LeafletFA(adata, K=20)
model.from_anndata()   # validate input and build tensors
model.train()          # variational inference
model.get_all_variables()

model.psi          # (K × junctions) — splicing program loadings
model.assign_post  # (cells × K)     — cell factor activities
model.pi           # (K,)            — factor prevalences

See LeafletFA model for the full parameter reference and SplicingDataset format for the expected input structure.