Abstract

BackgroundBiological regulatory networks, representing the interactions between genes and their products, control almost every biological activity in the cell. Shortest path search is critical to apprehend the structure of these networks, and to detect their key components. Counting the number of shortest paths between pairs of genes in biological networks is a polynomial time problem. The fact that biological interactions are uncertain events however drastically complicates the problem, as it makes the topology of a given network uncertain.ResultsIn this paper, we develop a novel method to count the number of shortest paths between two nodes in probabilistic networks. Unlike earlier approaches, which uses the shortest path counting methods that are specifically designed for deterministic networks, our method builds a new mathematical model to express and compute the number of shortest paths. We prove the correctness of this model.ConclusionsWe compare our novel method to three existing shortest path counting methods on synthetic and real gene regulatory networks. Our experiments demonstrate that our method is scalable, and it outperforms the existing methods in accuracy. Application of our shortest path counting method to detect communities in probabilistic networks shows that our method successfully finds communities in probabilistic networks. Moreover, our experiments on cell cycle pathway among different cancer types exhibit that our method helps in uncovering key functional characteristics of biological networks.

Highlights

  • Biological regulatory networks, representing the interactions between genes and their products, control almost every biological activity in the cell

  • A measure of the number of shortest paths that go through each edge, describes the essentiality of the underlying gene-to-gene interactions, and helps us to discover the bottlenecks in the biological systems [15]

  • We develop a novel method to count the shortest paths between a pair of nodes in probabilistic networks

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Summary

Introduction

Biological regulatory networks, representing the interactions between genes and their products, control almost every biological activity in the cell. The fact that biological interactions are uncertain events drastically complicates the problem, as it makes the topology of a given network uncertain Biological molecules such as proteins and metabolites work together to deliver specific functions inside the cell. Biological networks share structural properties that are often informative to discover the key components of the biological systems and their functional roles. One such characteristic property is the set of ‘shortest paths’ connecting two given molecules on the network. A measure of the number of shortest paths that go through each edge, describes the essentiality of the underlying gene-to-gene interactions, and helps us to discover the bottlenecks in the biological systems [15].

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