Introducing the novel Cytoscape app TimeNexus to analyze time-series data using temporal MultiLayer Networks (tMLNs)

Abstract

Integrating -omics data with biological networks such as protein–protein interaction networks is a popular and useful approach to interpret expression changes of genes in changing conditions, and to identify relevant cellular pathways, active subnetworks or network communities. Yet, most -omics data integration tools are restricted to static networks and therefore cannot easily be used for analyzing time-series data. Determining regulations or exploring the network structure over time requires time-dependent networks which incorporate time as one component in their structure. Here, we present a method to project time-series data on sequential layers of a multilayer network, thus creating a temporal multilayer network (tMLN). We implemented this method as a Cytoscape app we named TimeNexus. TimeNexus allows to easily create, manage and visualize temporal multilayer networks starting from a combination of node and edge tables carrying the information on the temporal network structure. To allow further analysis of the tMLN, TimeNexus creates and passes on regular Cytoscape networks in form of static versions of the tMLN in three different ways: (i) over the entire set of layers, (ii) over two consecutive layers at a time, (iii) or on one single layer at a time. We combined TimeNexus with the Cytoscape apps PathLinker and AnatApp/ANAT to extract active subnetworks from tMLNs. To test the usability of our app, we applied TimeNexus together with PathLinker or ANAT on temporal expression data of the yeast cell cycle and were able to identify active subnetworks relevant for different cell cycle phases. We furthermore used TimeNexus on our own temporal expression data from a mouse pain assay inducing hindpaw inflammation and detected active subnetworks relevant for an inflammatory response to injury, including immune response, cell stress response and regulation of apoptosis. TimeNexus is freely available from the Cytoscape app store at https://apps.cytoscape.org/apps/TimeNexus.

Construction of a competing endogenous RNA network in head and neck squamous cell carcinoma by pan-cancer analysis

“…To improve accuracy, the predicted miRNAs were selected as the upstream miRNAs of SFXN3 when they were identified by no less than two prediction programs. A total of 32 miRNAs were identified as the upstream miRNAs of SFXN3 , and they were subsequently used to construct a miRNA-mRNA action network using Cytoscape ( 16 ) ( Figure 3 ).…”

Network Analysis Reveals the Molecular Bases of Statin Pleiotropy That Vary with Genetic Background

“…The resulting protein-protein interaction network was a first-order network representing the input nodes with their direct interactors (path length 1), which was then augmented into a second-order network to include nodes that connected the input genes as well as nodes that were interactors (of path length 2), but which only included the minimum number of nodes necessary to maintain connectivity of the network (minimum network). The gene-gene interaction networks (GINs) and the protein-protein interaction networks (PPINs) were then integrated into a single multilayer network using TimeNexus ( 92 ) in Cytoscape ( 93 ).…”

Phasik: a Python package to identify system states in partially temporal networks

“…In C, P. Holme provides a fast implementation of the susceptible-infected-recovered (SIR) epidemic model on temporal networks (Holme, 2021). TimeNexus (Pierrelée et al, 2021) is a general-purpose Cytoscape app for temporal networks with emphasis on modeling gene expression data.…”