OCSANA+

OCSANA+ is a Cytoscape app for identifying driver nodes that control non-linear systems’ long-term dynamics, prioritizing combinations of interventions in large scale complex networks, and estimating the effects of node perturbations in signaling networks, all based on the analysis of the network’s structure. OCSANA+ includes an update to the previously introduced OCSANA (optimal combinations of interventions from network analysis) software tool with cutting-edge and rigorously tested algorithms, together with recently-developed structure-based control algorithms for non-linear systems and an algorithm for estimating the signal flow. All these algorithms are based on the network’s topology.

OCSANA+ features:

Optimal Combinations of Interventions OCSANA (Optimal Combinations of Interventions from Network Analysis), originally introduced in Vera-Licona et al., 2013, identifies and prioritizes optimal minimal combinations of interventions (CIs) that disrupt the elementary paths from selected source nodes to the specified target nodes. When indicated by the user, OCSANA seeks to additionally minimize the side-effects that CIs can cause on specified off-target nodes.

Feedback Vertex Set Control Feedback Vertex Set Control (FC) is an attractor based control method specifically developed for networks with non-linear dynamics that uses a component of the network’s topology, the Feedback Vertex Set (FVS) (Mochizuki et al., 2013 )The FVS of a network is defined as the minimal set of nodes whose removal would leave a graph without cycles. Later, an extended FC control version adding the the network’s source nodes was proposed by Zanudo et al., 2017.

Signal Flow Analysis The SFA algorithm (Lee and Cho, 2018) estimates the steady state activity of a node by a linear difference equation that considers (i) The activity of a node at the previous time step, (ii) The effect (activating or inhibiting) and influence of incoming edges to a node, and (iii) the initial activities of the node

In this manual we include instructions for intallation, CI discovery, FC identification, SFA analysis, and a walkthrough tutorial of the features of OCSANA+.

User Guide

• Installing OCSANA+
• Computing Optimal Combinations of Intervention with OCSANA
  • Running OCSANA in Cytoscape
  • OCSANA Results
• Identifying Minimal Feedback Vertex Set Control (FC) Sets
  • Running FC in Cytoscape
  • FC Results
• Performing Topological Estimation of Signal Flow with Signal Flow Analysis (SFA)
  • Running SFA in Cytoscape
  • SFA Results
• Walk-Through Example: Cell Fate Specification in Ascidian Embryo
  • Step 1: Initial Cytoscape Setup
  • Step 2: Identifying Feedback Vertex Set Control Sets (FC)
  • Step 3: Simulating FC node perturbations using SFA
  • Identifying Feedback Vertex Set Control Sets (FC) with source nodes
  • Identifying CIs with OCSANA
  • Simulating FC and CI node perturbations using SFA