FIREFate (Functional and Interpretable Regulatory Encoding of cellular Fate)

This repository provides an open-source toolkit, which delivers multi-scale insights at the cell-population, gene-regulatory and epigenomic levels to predict fate-bias during cell state transitions, and infer regulatory components governing cell fate decisions. The framework is built for single-cell (sc-snRNA/scATAC-seq) datasets for both matched or un-matched multi-omic sequenced populations.

Downstream tasks include -

1. Discovery of interpretable cellular programs (CPs) underlying phenotypically-contrasting cell states, arising from natural progression of cellular processes or fate-biasing interventions.

2. Prediction of fate-biased cell populations in uncommitted states during differentiation, using CPs inferred from intervention datasets (TF-KO)

3. Construction of State-Specific GRNs, and a combined cross-state GRN whose connectivity spans both states in (1), for enrichment of Transcription Factor (TF) activity, which regulates the CP encoding the discriminative phenotype between states.

4. Construction of Transition-Window-Specific GRNs, with clustered regulatory edges to temporally order waves of TF regulation.

5. Construction of Episodic GRNs that capture TF–target forces held temporally invariant across each episode, for enrichment of dynamic TF epigenomic and regulatory activity within each CP, underlying cell fate.

6. Quantification of in-silico perturbation effects from state-specific (DONE) /dynamic phenotypic shifts (TO-DO) induced by perturbing enriched TFs.

Documentation

User guide and API reference are built with Sphinx and hosted on Read the Docs (configure the project at readthedocs.org to point at this repository; the config file is .readthedocs.yaml). After publishing, the site is typically available at https://firefate.readthedocs.io/ when the project slug is firefate.

To build the HTML docs locally:

pip install ".[docs]"
sphinx-build -W -b html docs docs/_build/html