MOTIVATION: As RNA interference is becoming a standard method for targeted gene perturbation, computational approaches to reverse engineer parts of biological networks based on measurable effects of RNAi become increasingly relevant. The vast majority of these methods use gene expression data, but little attention has been paid so far to other data types. RESULTS: Here we present a method, which can infer gene networks from high-dimensional phenotypic perturbation effects on single cells recorded by time-lapse microscopy. We use data from the Mitocheck project to extract multiple shape, intensity and texture features at each frame. Features from different cells and movies are then aligned along the cell cycle time. Subsequently we use Dynamic Nested Effects Models (dynoNEMs) to estimate parts of the network structure between perturbed genes via a Markov Chain Monte Carlo approach. Our simulation results indicate a high reconstruction quality of this method. A reconstruction based on 22 gene knock downs yielded a network, where all edges could be explained via the biological literature. AVAILABILITY: The implementation of dynoNEMs is part of the Bioconductor R-package nem.

MOTIVATION: Targeted interventions in combination with the measurement of secondary effects can be used to computationally reverse engineer features of upstream non-transcriptional signaling cascades. Nested effect models (NEMs) have been introduced as a statistical approach to estimate the upstream signal flow from downstream nested subset structure of perturbation effects. The method was substantially extended later on by several authors and successfully applied to various datasets. The connection of NEMs to Bayesian Networks and factor graph models has been highlighted. RESULTS: Here, we introduce a computationally attractive extension of NEMs that enables the analysis of perturbation time series data, hence allowing to discriminate between direct and indirect signaling and to resolve feedback loops. AVAILABILITY: The implementation (R and C) is part of the Supplement to this article.