Abstract

BackgroundAligning protein-protein interaction (PPI) networks is very important to discover the functionally conserved sub-structures between different species. In recent years, the global PPI network alignment problem has been extensively studied aiming at finding the one-to-one alignment with the maximum matching score. However, finding large conserved components remains challenging due to its NP-hardness.ResultsWe propose a new graph matching method GMAlign for global PPI network alignment. It first selects some pairs of important proteins as seeds, followed by a gradual expansion to obtain an initial matching, and then it refines the current result to obtain an optimal alignment result iteratively based on the vertex cover. We compare GMAlign with the state-of-the-art methods on the PPI network pairs obtained from the largest BioGRID dataset and validate its performance. The results show that our algorithm can produce larger size of alignment, and can find bigger and denser common connected subgraphs as well for the first time. Meanwhile, GMAlign can achieve high quality biological results, as measured by functional consistency and semantic similarity of the Gene Ontology terms. Moreover, we also show that GMAlign can achieve better results which are structurally and biologically meaningful in the detection of large conserved biological pathways between species.ConclusionsGMAlign is a novel global network alignment tool to discover large conserved functional components between PPI networks. It also has many potential biological applications such as conserved pathway and protein complex discovery across species. The GMAlign software and datasets are avaialbile at https://github.com/yzlwhu/GMAlign.

Highlights

  • Aligning protein-protein interaction (PPI) networks is very important to discover the functionally conserved sub-structures between different species

  • We model the global PPI network alignment problem as graph matching, which aims to find a matching M between G1 and G2 according to the mapping relationship f, i.e., M =

  • Detecting conserved pathways We further evaluate the algorithms by the detection of functional conserved pathways on the largest PPI networks, human (SC) and yeast (HS), which have been investigated a lot in the literature [2, 23, 25, 26]

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Summary

Introduction

Aligning protein-protein interaction (PPI) networks is very important to discover the functionally conserved sub-structures between different species. The global PPI network alignment problem has been extensively studied aiming at finding the one-to-one alignment with the maximum matching score. Some local network alignment methods were developed to reveal conserved components like pathways or protein complexes between species, such as PathBLAST [13], Graemlin [14], and MaWISh [15]. MaWISh [15] extends some concepts in sequence alignment such as match, mismatch and gap, and models it as a maximum weight induced subgraph problem where the structure similarity is measured based on the evolutionary events. Most of the studies focus on the pairwise global alignment to maximize the overall matching between networks. We mainly introduce pairwise global network aligners

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