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BinAligner: a heuristic method to align biological networks.

ABSTRACT: The advances in high throughput omics technologies have made it possible to characterize molecular interactions within and across various species. Alignments and comparison of molecular networks across species will help detect orthologs and conserved functional modules and provide insights on the evolutionary relationships of the compared species. However, such analyses are not trivial due to the complexity of network and high computational cost. Here we develop a mixture of global and local algorithm, BinAligner, for network alignments. Based on the hypotheses that the similarity between two vertices across networks would be context dependent and that the information from the edges and the structures of subnetworks can be more informative than vertices alone, two scoring schema, 1-neighborhood subnetwork and graphlet, were introduced to derive the scoring matrices between networks, besides the commonly used scoring scheme from vertices. Then the alignment problem is formulated as an assignment problem, which is solved by the combinatorial optimization algorithm, such as the Hungarian method. The proposed algorithm was applied and validated in aligning the protein-protein interaction network of Kaposi's sarcoma associated herpesvirus (KSHV) and that of varicella zoster virus (VZV). Interestingly, we identified several putative functional orthologous proteins with similar functions but very low sequence similarity between the two viruses. For example, KSHV open reading frame 56 (ORF56) and VZV ORF55 are helicase-primase subunits with sequence identity 14.6%, and KSHV ORF75 and VZV ORF44 are tegument proteins with sequence identity 15.3%. These functional pairs can not be identified if one restricts the alignment into orthologous protein pairs. In addition, BinAligner identified a conserved pathway between two viruses, which consists of 7 orthologous protein pairs and these proteins are connected by conserved links. This pathway might be crucial for virus packing and infection.

SUBMITTER: Yang J

PROVIDER: S-EPMC3851320 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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BinAligner: a heuristic method to align biological networks.

Yang Jialiang J Li Jun J Grünewald Stefan S Wan Xiu-Feng XF

BMC bioinformatics 20131009

The advances in high throughput omics technologies have made it possible to characterize molecular interactions within and across various species. Alignments and comparison of molecular networks across species will help detect orthologs and conserved functional modules and provide insights on the evolutionary relationships of the compared species. However, such analyses are not trivial due to the complexity of network and high computational cost. Here we develop a mixture of global and local alg ...[more]

PMID: 24266981

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Project description:With the development of high throughput technologies, there are more and more protein-protein interaction (PPI) networks available, which provide a need for efficient computational tools for network alignment. Network alignment is widely used to predict functions of certain proteins, identify conserved network modules, and study the evolutionary relationship across species or biological entities. However, network alignment is an NP-complete problem, and previous algorithms are usually slow or less accurate in aligning big networks like human vs. yeast. In this study, we proposed a fast yet accurate algorithm called Network Alignment by Integrating Biological Process (NAIGO). Specifically, we first divided the networks into subnets taking the advantage of known prior knowledge, such as gene ontology. For each subnet pair, we then developed a novel method to align them by considering both protein orthologous information and their local structural information. After that, we expanded the obtained local network alignments in a greedy manner. Taking the aligned pairs as seeds, we formulated the global network alignment problem as an assignment problem based on similarity matrix, which was solved by the Hungarian method. We applied NAIGO to align human and Saccharomyces cerevisiae S288c PPI network and compared the results with other popular methods like IsoRank, GRAAL, SANA, and NABEECO. As a result, our method outperformed the competitors by aligning more orthologous proteins or matched interactions. In addition, we found a few potential functional orthologous proteins such as RRM2B in human and DNA2 in S. cerevisiae S288c, which are related to DNA repair. We also identified a conserved subnet with six orthologous proteins EXO1, MSH3, MSH2, MLH1, MLH3, and MSH6, and six aligned interactions. All these proteins are associated with mismatch repair. Finally, we predicted a few proteins of S. cerevisiae S288c potentially involving in certain biological processes like autophagosome assembly.

Dataset Information

BinAligner: a heuristic method to align biological networks.

Publications

BinAligner: a heuristic method to align biological networks.

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