Navigating differential structures in complex networks

TL;DR

This paper introduces a new theory and method for characterizing shared structural roles of nodes across multiple networks, enabling interpretable insights into differential network structures, especially in gene co-expression studies.

Contribution

It provides a novel, interpretable approach for analyzing shared node roles across networks, with proven accuracy and applicability to complex biological data.

Findings

Method accurately characterizes shared node roles in simulated benchmarks.

It reveals nuanced differences in gene networks under different conditions.

Supports analysis of up to 100 networks simultaneously.

Abstract

Structural changes in a network representation of a system (e.g.,different experimental conditions, time evolution), can provide insight on its organization, function and on how it responds to external perturbations. The deeper understanding of how gene networks cope with diseases and treatments is maybe the most incisive demonstration of the gains obtained through this differential network analysis point-of-view, which lead to an explosion of new numeric techniques in the last decade. However, {\it where} to focus ones attention, or how to navigate through the differential structures can be overwhelming even for few experimental conditions. In this paper, we propose a theory and a methodological implementation for the characterization of shared "structural roles" of nodes simultaneously within and between networks, whose outcome is a highly {\em interpretable} map. The main features and accuracy are investigated with numerical benchmarks generated by a stochastic block model. Results show that it can provide nuanced and interpretable information in scenarios with very different (i) community sizes and (ii) total number of communities, and (iii) even for a large number of 100 networks been compared (e.g., for 100 different experimental conditions). Then, we show evidence that the strength of the method is its "story-telling"-like characterization of the information encoded in a set of networks, which can be used to pinpoint unexpected differential structures, leading to further investigations and providing new insights. We provide an illustrative, exploratory analysis of four gene co-expression networks from two cell types $\times$ two treatments (interferon-$\beta$ stimulated or control). The method proposed here allowed us to elaborate and test a set of very specific hypotheses related to {\em unique} and {\em subtle} nuances of the structural differences between these networks.