This repository contains all the model code used in BuDDI: Bulk Deconvolution with Domain Invariance to predict cell-type-specific perturbations from bulk
A tutorial, as well as all code needed to reproduce the figures from the manuscript, are provided in this companion repository: https://github.com/greenelab/buddi_analysis
While single-cell experiments provide deep cellular resolution within a single sample, some are inherently more challenging than bulk experiments due to dissociation difficulties, cost, or limited tissue availability. This creates a situation where we have deep cellular profiles of one sample or condition, and bulk profiles across multiple samples and conditions.
A schematic of what BuDDi's methodological goal is shown below:
To bridge this gap, we propose BuDDI (BUlk Deconvolution with Domain Invariance).
BuDDI utilizes domain adaptation techniques to effectively integrate available corpora of case-control bulk and reference scRNA-seq observations to infer cell-type-specific perturbation effects. BuDDI achieves this by learning independent latent spaces within a single variational autoencoder (VAE) encompassing at least four sources of variability: 1) cell-type proportion, 2) perturbation effect, 3) structured experimental variability, and 4) remaining variability. Since each latent space is encouraged to be independent, we simulate perturbation responses by independently composing each latent space to simulate cell-type-specific perturbation responses.
Below is a schematic of the VAE structure of BuDDI:
First, you need to install dependencies using your package manager. Below is an example for OS X using brew.
brew install hdf5 c-blosc cython
export HDF5_DIR=/opt/homebrew/opt/hdf5
export BLOSC_DIR=/opt/homebrew/opt/c-bloscSecond, you will install BuDDI from github using pip. It is recommended that you install this into a virtual env that you can activate before running the provided analysis scripts or your own BuDDI experiments.
pip install git+https://github.com/greenelab/buddi.gitSee the tutorial for detailed instructions on how to use BuDDI.
To import BuDDI and its helper methods in your notebook, simply add the following
from buddi import buddi
from buddi.preprocessing import sc_preprocess
from buddi.plotting import validation_plotting as vp