Phylogenetic analysis of modularity in protein interaction networks

BackgroundIn systems biology, comparative analyses of molecular interactions across diverse species indicate that conservation and divergence of networks can be used to understand functional evolution from a systems perspective. A key characteristic of these networks is their modularity, which contributes significantly to their robustness, as well as adaptability. Consequently, analysis of modular network structures from a phylogenetic perspective may be useful in understanding the emergence, conservation, and diversification of functional modularity.ResultsIn this paper, we propose a phylogenetic framework for analyzing network modules, with applications that extend well beyond network-based phylogeny reconstruction. Our approach is based on identification of modular network components from each network separately, followed by projection of these modules onto the networks of other species to compare different networks. Subsequently, we use the conservation of various modules in each network to assess the similarity between different networks. Compared to traditional methods that rely on topological comparisons, our approach has key advantages in (i) avoiding intractable graph comparison problems in comparative network analysis, (ii) accounting for noise and missing data through flexible treatment of network conservation, and (iii) providing insights on the evolution of biological systems through investigation of the evolutionary trajectories of network modules. We test our method, MOPHY, on synthetic data generated by simulation of network evolution, as well as existing protein-protein interaction data for seven diverse species. Comprehensive experimental results show that MOPHY is promising in reconstructing evolutionary histories of extant networks based on conservation of modularity, it is highly robust to noise, and outperforms existing methods that quantify network similarity in terms of conservation of network topology.ConclusionThese results establish modularity and network proximity as useful features in comparative network analysis and motivate detailed studies of the evolutionary histories of network modules.

[1]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[2]  G. Sumara,et al.  A Probabilistic Functional Network of Yeast Genes , 2004 .

[3]  Ananth Grama,et al.  Functional coherence in domain interaction networks , 2008, ECCB.

[4]  T. Ideker,et al.  Modeling cellular machinery through biological network comparison , 2006, Nature Biotechnology.

[5]  M. Nei,et al.  Molecular Evolution and Phylogenetics , 2000 .

[6]  R. Karp,et al.  From the Cover : Conserved patterns of protein interaction in multiple species , 2005 .

[7]  Jie Zheng,et al.  Support for the Coelomata clade of animals from a rigorous analysis of the pattern of intron conservation. , 2007, Molecular biology and evolution.

[8]  B. Snel,et al.  Toward Automatic Reconstruction of a Highly Resolved Tree of Life , 2006, Science.

[9]  Bonnie Berger,et al.  Global alignment of multiple protein interaction networks with application to functional orthology detection , 2008, Proceedings of the National Academy of Sciences.

[10]  Jiong Yang,et al.  PathFinder: mining signal transduction pathway segments from protein-protein interaction networks , 2007, BMC Bioinformatics.

[11]  Tamir Tuller,et al.  Biological Networks: Comparison, Conservation, and Evolutionary Trees , 2006, RECOMB.

[12]  Antal F. Novak,et al.  networks Græmlin : General and robust alignment of multiple large interaction data , 2006 .

[13]  Dong-Guk Shin,et al.  Nodal distance algorithm: calculating a phylogenetic tree comparison metric , 2003, Third IEEE Symposium on Bioinformatics and Bioengineering, 2003. Proceedings..

[14]  Gary D. Bader,et al.  An automated method for finding molecular complexes in large protein interaction networks , 2003, BMC Bioinformatics.

[15]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[16]  P. Uetz,et al.  What do we learn from high-throughput protein interaction data? , 2004, Expert review of proteomics.

[17]  Colin Cooper,et al.  Improved Duplication Models for Proteome Network Evolution , 2005, Systems Biology and Regulatory Genomics.

[18]  D. Goldberg,et al.  Assessing experimentally derived interactions in a small world , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Kitano.  Systems Biology: A Brief Overview , 2002, Science.

[20]  Olivier Gascuel,et al.  Mathematics of Evolution and Phylogeny , 2005 .

[21]  Serafim Batzoglou,et al.  Automatic Parameter Learning for Multiple Network Alignment , 2008, RECOMB.

[22]  Alessandro Vespignani,et al.  Evolution thinks modular , 2003, Nature Genetics.

[23]  R. Sharan,et al.  Network-based prediction of protein function , 2007, Molecular systems biology.

[24]  Bonnie Berger,et al.  Global Alignment of Multiple Protein Interaction Networks , 2008, Pacific Symposium on Biocomputing.

[25]  A. Vespignani,et al.  Modeling of Protein Interaction Networks , 2001, Complexus.

[26]  Wojciech Szpankowski,et al.  Detecting Conserved Interaction Patterns in Biological Networks , 2006, J. Comput. Biol..

[27]  Susumu Goto,et al.  Extraction of phylogenetic network modules from prokayrote metabolic pathways. , 2004, Genome informatics. International Conference on Genome Informatics.

[28]  R. Solé,et al.  Evolving protein interaction networks through gene duplication. , 2003, Journal of theoretical biology.

[29]  R. Karp,et al.  Conserved pathways within bacteria and yeast as revealed by global protein network alignment , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Ioannis Xenarios,et al.  DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions , 2002, Nucleic Acids Res..

[31]  D. Robinson,et al.  Comparison of phylogenetic trees , 1981 .

[32]  Jason A. Papin,et al.  Reconstruction of cellular signalling networks and analysis of their properties , 2005, Nature Reviews Molecular Cell Biology.

[33]  Srinivas Aluru,et al.  Handbook Of Computational Molecular Biology , 2010 .

[34]  Sourav Bandyopadhyay,et al.  Systematic identification of functional orthologs based on protein network comparison. , 2006, Genome research.

[35]  Z N Oltvai,et al.  Evolutionary conservation of motif constituents in the yeast protein interaction network , 2003, Nature Genetics.

[36]  C. Randal Linder,et al.  An Overview of Phylogeny Reconstruction , 2005 .

[37]  E. Ziv,et al.  Inferring network mechanisms: the Drosophila melanogaster protein interaction network. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[38]  L. Mirny,et al.  Protein complexes and functional modules in molecular networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.