Abstract

In this work, we introduce a novel network synthesis model that can generate families of evolutionarily related synthetic protein–protein interaction (PPI) networks. Given an ancestral network, the proposed model generates the network family according to a hypothetical phylogenetic tree, where the descendant networks are obtained through duplication and divergence of their ancestors, followed by network growth using network evolution models. We demonstrate that this network synthesis model can effectively create synthetic networks whose internal and cross-network properties closely resemble those of real PPI networks. The proposed model can serve as an effective framework for generating comprehensive benchmark datasets that can be used for reliable performance assessment of comparative network analysis algorithms. Using this model, we constructed a large-scale network alignment benchmark, called NAPAbench, and evaluated the performance of several representative network alignment algorithms. Our analysis clearly shows the relative performance of the leading network algorithms, with their respective advantages and disadvantages. The algorithm and source code of the network synthesis model and the network alignment benchmark NAPAbench are publicly available at http://www.ece.tamu.edu/bjyoon/NAPAbench/.

Highlights

  • Protein-protein interactions (PPIs) lie at the core of a wide range of biological processes in cells, including transcriptional, signaling, and metabolic processes [1]

  • A large number of computational methods have been developed for comparative analysis of biological networks, where their main focus has been on the identification of functional modules that are conserved in the networks of multiple species [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]

  • The scaling and shape parameters of the Gamma distributions in (2) were set to ko~0:72, ho~226, kn~0:85, hn~73, and the exponent b in the distribution Pc(l) was set to b~1:6, such that the cross-network properties between G1 and G2 resemble those between the D. melanogaster PPI network and the S. cerevisiae PPI network

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Summary

Introduction

Protein-protein interactions (PPIs) lie at the core of a wide range of biological processes in cells, including transcriptional, signaling, and metabolic processes [1]. Erten et al [52] proposed a simulation scheme for generating a set of networks with known phylogeny, where the driving motivation was to evaluate the accuracy of their network-based phylogeny reconstruction algorithm These studies [51,52] serve as interesting showcases of the important role of synthetic network models. The model presented in [51] cannot be used to synthesize a network family with an arbitrary phylogeny Both models in [51] and [52] do not explicitly represent the functional correspondence between individual proteins across different networks, which is indispensable for evaluating the accuracy of network alignment algorithms. To demonstrate the utility of the network synthesis model, we created a comprehensive network alignment benchmark based on the proposed model and carried out an extensive performance analysis of select state-of-the-art network alignment algorithms

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