Single cell network analysis with a mixture of Nested Effects Models

    loading  Checking for direct PDF access through Ovid

Abstract

Motivation

New technologies allow for the elaborate measurement of different traits of single cells under genetic perturbations. These interventional data promise to elucidate intra-cellular networks in unprecedented detail and further help to improve treatment of diseases like cancer. However, cell populations can be very heterogeneous.

Results

We developed a mixture of Nested Effects Models (M&NEM) for single-cell data to simultaneously identify different cellular subpopulations and their corresponding causal networks to explain the heterogeneity in a cell population. For inference, we assign each cell to a network with a certain probability and iteratively update the optimal networks and cell probabilities in an Expectation Maximization scheme. We validate our method in the controlled setting of a simulation study and apply it to three data sets of pooled CRISPR screens generated previously by two novel experimental techniques, namely Crop-Seq and Perturb-Seq.

Availability and implementation

The mixture Nested Effects Model (M&NEM) is available as the R-package mnem at https://github.com/cbg-ethz/mnem/.

Supplementary information

Supplementary data are available at Bioinformatics online.

Related Topics

    loading  Loading Related Articles