Single cell network analysis with a mixture of Nested Effects Models


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Abstract

MotivationNew 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.ResultsWe 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 implementationThe mixture Nested Effects Model (M&NEM) is available as the R-package mnem at https://github.com/cbg-ethz/mnem/.Supplementary informationSupplementary data are available at Bioinformatics online.

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