NetprioR: a probabilistic model for integrative hit prioritisation of genetic screens.

Abstract

In the post-genomic era of big data in biology, computational approaches to integrate multiple heterogeneous data sets become increasingly important. Despite the availability of large amounts of omics data, the prioritisation of genes relevant for a specific functional pathway based on genetic screening experiments, remains a challenging task. Here, we introduce netprioR, a probabilistic generative model for semi-supervised integrative prioritisation of hit genes. The model integrates multiple network data sets representing gene-gene similarities and prior knowledge about gene functions from the literature with gene-based covariates, such as phenotypes measured in genetic perturbation screens, for example, by RNA interference or CRISPR/Cas9. We evaluate netprioR on simulated data and show that the model outperforms current state-of-the-art methods in many scenarios and is on par otherwise. In an application to real biological data, we integrate 22 network data sets, 1784 prior knowledge class labels and 3840 RNA interference phenotypes in order to prioritise novel regulators of Notch signalling in Drosophila melanogaster. The biological relevance of our predictions is evaluated using in silico and in vivo experiments. An efficient implementation of netprioR is available as an R package at http://bioconductor.org/packages/netprioR.