Counting motifs in dynamic networks

BackgroundA network motif is a sub-network that occurs frequently in a given network. Detection of such motifs is important since they uncover functions and local properties of the given biological network. Finding motifs is however a computationally challenging task as it requires solving the costly subgraph isomorphism problem. Moreover, the topology of biological networks change over time. These changing networks are called dynamic biological networks. As the network evolves, frequency of each motif in the network also changes. Computing the frequency of a given motif from scratch in a dynamic network as the network topology evolves is infeasible, particularly for large and fast evolving networks.ResultsIn this article, we design and develop a scalable method for counting the number of motifs in a dynamic biological network. Our method incrementally updates the frequency of each motif as the underlying network’s topology evolves. Our experiments demonstrate that our method can update the frequency of each motif in orders of magnitude faster than counting the motif embeddings every time the network changes. If the network evolves more frequently, the margin with which our method outperforms the existing static methods, increases.ConclusionsWe evaluated our method extensively using synthetic and real datasets, and show that our method is highly accurate(≥ 96%) and that it can be scaled to large dense networks. The results on real data demonstrate the utility of our method in revealing interesting insights on the evolution of biological processes.

[1]  Tamer Kahveci,et al.  Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells , 2015, Genome research.

[2]  Sanjay Ranka,et al.  An Iterative Algorithm for Metabolic Network-Based Drug Target Identification , 2006, Pacific Symposium on Biocomputing.

[3]  M. Newman,et al.  On the uniform generation of random graphs with prescribed degree sequences , 2003, cond-mat/0312028.

[4]  Christian Böhm,et al.  Frequent subgraph discovery in dynamic networks , 2010, MLG '10.

[5]  Joshua A. Grochow,et al.  Network Motif Discovery Using Subgraph Enumeration and Symmetry-Breaking , 2007, RECOMB.

[6]  Jiong Yang,et al.  SPIN: mining maximal frequent subgraphs from graph databases , 2004, KDD.

[7]  Uri Alon,et al.  Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs , 2004, Bioinform..

[8]  Tamer Kahveci,et al.  Indexing a protein-protein interaction network expedites network alignment , 2015, BMC Bioinformatics.

[9]  F. Schreiber,et al.  MODA: an efficient algorithm for network motif discovery in biological networks. , 2009, Genes & genetic systems.

[10]  Alan M. Frieze,et al.  Random graphs , 2006, SODA '06.

[11]  Falk Schreiber,et al.  Frequency Concepts and Pattern Detection for the Analysis of Motifs in Networks , 2005, Trans. Comp. Sys. Biology.

[12]  Guimin Qin,et al.  Significant Substructure Discovery in Dynamic Networks , 2013 .

[13]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[14]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[15]  Christopher C. Moser,et al.  Natural engineering principles of electron tunnelling in biological oxidation–reduction , 1999, Nature.

[16]  Ambuj K. Singh,et al.  GraphSig: A Scalable Approach to Mining Significant Subgraphs in Large Graph Databases , 2009, 2009 IEEE 25th International Conference on Data Engineering.

[17]  Tamer Kahveci,et al.  Color distribution can accelerate network alignment , 2013, BCB.

[18]  Lawrence B. Holder,et al.  Substructure Discovery Using Minimum Description Length and Background Knowledge , 1993, J. Artif. Intell. Res..

[19]  Tamer Kahveci,et al.  Identification of large disjoint motifs in biological networks , 2016, BMC Bioinformatics.

[20]  S. Shen-Orr,et al.  Networks Network Motifs : Simple Building Blocks of Complex , 2002 .

[21]  George Karypis,et al.  An efficient algorithm for discovering frequent subgraphs , 2004, IEEE Transactions on Knowledge and Data Engineering.

[22]  David S. Johnson,et al.  Computers and Intractability: A Guide to the Theory of NP-Completeness , 1978 .

[23]  Sebastian Wernicke,et al.  Efficient Detection of Network Motifs , 2006, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[24]  Mong-Li Lee,et al.  NeMoFinder: dissecting genome-wide protein-protein interactions with meso-scale network motifs , 2006, KDD '06.

[25]  Sahar Asadi,et al.  Kavosh: a new algorithm for finding network motifs , 2009, BMC Bioinformatics.

[26]  Roded Sharan,et al.  QNet: A Tool for Querying Protein Interaction Networks , 2007, RECOMB.

[27]  Jiawei Han,et al.  Mining coherent dense subgraphs across massive biological networks for functional discovery , 2005, ISMB.

[28]  George Karypis,et al.  GREW - a scalable frequent subgraph discovery algorithm , 2004, Fourth IEEE International Conference on Data Mining (ICDM'04).

[29]  Jiawei Han,et al.  gSpan: graph-based substructure pattern mining , 2002, 2002 IEEE International Conference on Data Mining, 2002. Proceedings..

[30]  C. Francke,et al.  Reconstructing the metabolic network of a bacterium from its genome. , 2005, Trends in microbiology.

[31]  Sebastian Wernicke,et al.  A Faster Algorithm for Detecting Network Motifs , 2005, WABI.

[32]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[33]  Stephen A. Cook,et al.  The complexity of theorem-proving procedures , 1971, STOC.

[34]  Albert,et al.  Emergence of scaling in random networks , 1999, Science.

[35]  Tijana Milenkovic,et al.  GraphCrunch: A tool for large network analyses , 2008, BMC Bioinformatics.