LIONESS

Estimating sample-specific regulatory networks (also on the arXiv)

Biological systems are driven by intricate interactions among the complex array of molecules that comprise the cell. Many methods have been developed to reconstruct network models that attempt to capture those interactions. These methods often draw on large numbers of measured expression samples to tease out subtle signals and infer connections between genes (or gene products). The result is an aggregate network model representing a single estimate for edge likelihoods. While informative, aggregate models fail to capture the heterogeneity that is often represented in a population. Here we propose a method to reverse engineer sample-specific networks from aggregate network models. We demonstrate the accuracy and applicability of our approach in several datasets, including simulated data, microarray expression data from synchronized yeast cells, and RNA-seq data collected from human subjects. We show that these sample-specific networks can be used to study the evolution of network topology across time and to characterize shifts in gene regulation that may not be apparent in the expression data. We believe the ability to generate sample-specific networks will revolutionize the field of network biology and has the potential to usher in an era of precision network medicine.

lionessR: single sample network inference in R (also on the bioRxiv)

Background: In biomedical research, network inference algorithms are typically used to infer complex association patterns between biological entities, such as between genes or proteins, using data from a population. This resulting aggregate network, in essence, averages over the networks of those individuals in the population. LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) is a method that can be used together with a network inference algorithm to extract networks for individual samples in a population. The method's key characteristic is that, by modeling networks for individual samples in a data set, it can capture network heterogeneity in a population. LIONESS was originally made available as a function within the PANDA (Passing Attributes between Networks for Data Assimilation) regulatory network reconstruction framework. However, the LIONESS algorithm is generalizable and can be used to model single sample networks based on a wide range of network inference algorithms. Results: In this software article, we describe lionessR, an R implementation of LIONESS that can be applied to any network inference method in R that outputs a complete, weighted adjacency matrix. As an example, we provide a vignette of an application of lionessR to model single sample networks based on correlated gene expression in a bone cancer dataset. We show how the tool can be used to identify differential patterns of correlation between two groups of patients. Conclusions: We developed lionessR, an open source R package to model single sample networks. We show how lionessR can be used to inform us on potential precision medicine applications in cancer. The lionessR package is a user-friendly tool to perform such analyses. The package, which includes a vignette describing the application, is freely available at: https://github.com/kuijjerlab/lionessR and at: http://bioconductor.org/packages/lionessR .