Skip to main content

Single cell embedded topic model for integrated scRNA-seq data analysis.

Project description

scETM: single-cell Embedded Topic Model

A generative topic model that facilitates integrative analysis of large-scale single-cell RNA sequencing data.

The full description of scETM and its application on published single cell RNA-seq datasets are available here.

This repository includes detailed instructions for installation and requirements, demos, and scripts used for the benchmarking of 7 other state-of-art methods.

Contents

1 Model Overview

(a) Probabilistic graphical model of scETM. We model the scRNA-profile read count matrix yd,g in cell d and gene g across S subjects or studies by a multinomial distribution with the rate parameterized by cell topic mixture θ, topic embedding α, gene embedding ρ, and batch effects λ. (b) Matrix factorization view of scETM. (c) Encoder architecture for inferring the cell topic mixture θ.

2 Installation

Python version: 3.7+ scETM is included in PyPI, so you can install it by

pip install scETM

To enable GPU computing (which significantly boosts the performance), please install PyTorch with GPU support before installing scETM.

3 Usage

A step-by-step scETM tutorial can be found in here.

Required data

scETM requires a cells-by-genes matrix adata as input, in the format of an AnnData object. Detailed description about AnnData can be found here.

By default, scETM looks for batch information in the 'batch_indices' column of the adata.obs DataFrame, and cell type identity in the 'cell_types' column. If your data stores the batch and cell type information in different columns, pass them to the batch_col and cell_type_col arguments, respectively, when calling scETM functions.

p-scETM

p-scETM is a variant of scETM where part or all of the the gene embedding matrix ρ is fixed to a pathways-by-genes matrix, which can be downloaded from the pathDIP4 pathway database. We only keep pathways that contain more than 5 genes.

If it is desired to fix the gene embedding matrix ρ during training, let trainable_gene_emb_dim be zero. In this case, the gene set used to train the model would be the intersection of the genes in the scRNA-seq data and the genes in the gene-by-pathway matrix. Otherwise, if trainable_gene_emb_dim is set to a positive value, all the genes in the scRNA-seq data would be kept.

from scETM import scETM, UnsupervisedTrainer, prepare_for_transfer
import anndata

# Prepare the source dataset, Mouse Pancreas
mp = anndata.read_h5ad("MousePancreas.h5ad")
# Initialize model
model = scETM(mp.n_vars, mp.obs.batch_indices.nunique(), enable_batch_bias=True)
# The trainer object will set up the random seed, optimizer, training and evaluation loop, checkpointing and logging.
trainer = UnsupervisedTrainer(model, mp, train_instance_name="MP", ckpt_dir="../results")
# Train the model on adata for 12000 epochs, and evaluate every 1000 epochs. Use 4 threads to sample minibatches.
trainer.train(n_epochs=12000, eval_every=1000, n_samplers=4)

# Load the target dataset, Human Pancreas
hp = anndata.read_h5ad('HumanPancreas.h5ad')
# Align the source dataset's gene names (which are mouse genes) to the target dataset (which are human genes)
mp_genes = mp.var_names.str.upper()
mp_genes.drop_duplicates(inplace=True)
# Generate a new model and a modified dataset from the previously trained model and the mp_genes
model, hp = prepare_for_transfer(model, hp, mp_genes,
	keep_tgt_unique_genes=True,    # Keep target-unique genes in the model and the target dataset
    fix_shared_genes=True          # Fix parameters related to shared genes in the model
)
# Instantiate another trainer to fine-tune the model
trainer = UnsupervisedTrainer(model, hp, train_instance_name="HP_all_fix", ckpt_dir="../results", init_lr=5e-4)
trainer.train(n_epochs=800, eval_every=200)

4 Benchmarking

The commands used for running Harmony, Scanorama, Seurat, scVAE-GM, scVI, LIGER, scVI-LD are available in the scripts folder.

Project details


Download files

Download the file for your platform. If you're not sure which to choose, learn more about installing packages.

Source Distribution

scETM-0.2.0.tar.gz (28.0 kB view hashes)

Uploaded Source

Built Distribution

scETM-0.2.0-py3-none-any.whl (29.4 kB view hashes)

Uploaded Python 3

Supported by

AWS AWS Cloud computing and Security Sponsor Datadog Datadog Monitoring Fastly Fastly CDN Google Google Download Analytics Microsoft Microsoft PSF Sponsor Pingdom Pingdom Monitoring Sentry Sentry Error logging StatusPage StatusPage Status page