Algorithms for Regular Tree Grammar Network Search and Their Application to Mining Human-Viral Infection Patterns

Network querying is a powerful approach to mine molecular interaction networks. Most network querying tools support queries in the form of a template sub-network, in case of topology-constrained queries, or a set of colored vertices in case of topology-free queries. A third approach is grammar-based queries, which are more flexible and expressive as they allow the addition of logic rules to the query. Previous grammar-based querying tools defined queries via string grammars and identified paths in graphs. In this paper, we extend the scope of grammar-based queries to regular tree grammar (RTG), and the scope of the identified sub-graphs from paths to trees. We introduce a new problem and propose a novel algorithm to search a given graph for the k highest scoring sub-graphs matching a tree accepted by an RTG. Our algorithm is based on dynamic programming and combines an extension to k-best parsing optimization with color coding. We implement the new algorithm and exemplify its application to mining the human-viral interaction network. Our code is available at http://www.cs.bgu.ac.il/~smolyi/RTGnet/.

[1]  Walter Fiers,et al.  Interferon-Inducible Protein Mx1 Inhibits Influenza Virus by Interfering with Functional Viral Ribonucleoprotein Complex Assembly , 2012, Journal of Virology.

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

[3]  R. Belshe,et al.  Implications of the emergence of a novel H1 influenza virus. , 2009, The New England journal of medicine.

[4]  Steven Gygi,et al.  Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  David Chiang,et al.  Better k-best Parsing , 2005, IWPT.

[6]  Gaetano T. Montelione,et al.  Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus , 2011, Proceedings of the National Academy of Sciences.

[7]  Ron Y. Pinter,et al.  Alignment of metabolic pathways , 2005, Bioinform..

[8]  Osamu Takeuchi,et al.  TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity , 2007, Nature.

[9]  Hubert Comon,et al.  Tree automata techniques and applications , 1997 .

[10]  Hideyuki Konishi,et al.  UbcH8 regulates ubiquitin and ISG15 conjugation to RIG-I. , 2008, Molecular immunology.

[11]  Petteri Sevon,et al.  Subgraph Queries by Context-free Grammars , 2008, J. Integr. Bioinform..

[12]  Cristina G. Fernandes,et al.  Motif Search in Graphs: Application to Metabolic Networks , 2006, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[13]  Giulio Superti-Furga,et al.  Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins , 2013, Nature.

[14]  A V Finkelstein,et al.  Computation of biopolymers: a general approach to different problems. , 1993, Bio Systems.

[15]  Christoph H Emmerich,et al.  Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. , 2009, Molecular cell.

[16]  Roded Sharan,et al.  QPath: a method for querying pathways in a protein-protein interaction network , 2006, BMC Bioinformatics.

[17]  James Henderson,et al.  Faster cube pruning , 2010, IWSLT.

[18]  Jianzhong Li,et al.  Adding regular expressions to graph reachability and pattern queries , 2011, ICDE 2011.

[19]  A. Barabasi,et al.  Network medicine : a network-based approach to human disease , 2010 .

[20]  Joachim Niehren,et al.  Minimizing Tree Automata for Unranked Trees , 2005, DBPL.

[21]  Gabriel Pineda,et al.  Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. , 2006, Molecular cell.

[22]  N. Hacohen,et al.  A Physical and Regulatory Map of Host-Influenza Interactions Reveals Pathways in H1N1 Infection , 2009, Cell.

[23]  Roded Sharan,et al.  Topology-Free Querying of Protein Interaction Networks , 2009, RECOMB.

[24]  Ulf Leser,et al.  Regular Path Queries on Large Graphs , 2012, SSDBM.

[25]  Alberto O. Mendelzon,et al.  Finding Regular Simple Paths in Graph Databases , 1989, SIAM J. Comput..

[26]  Roded Sharan,et al.  Efficient Algorithms for Detecting Signaling Pathways in Protein Interaction Networks , 2006, J. Comput. Biol..

[27]  Yann Ponty,et al.  A Combinatorial Framework for Designing (Pseudoknotted) RNA Algorithms , 2011, WABI.

[28]  Joachim Niehren,et al.  Querying Unranked Trees with Stepwise Tree Automata , 2004, RTA.

[29]  Kazuhiro Iwai,et al.  Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. , 2011, Molecular cell.

[30]  S. Inoue,et al.  Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. , 2009, Cell host & microbe.

[31]  Noga Alon,et al.  Color-coding , 1995, JACM.

[32]  Susumu Goto,et al.  Data, information, knowledge and principle: back to metabolism in KEGG , 2013, Nucleic Acids Res..

[33]  Robert Patro,et al.  Predicting protein interactions via parsimonious network history inference , 2013, Bioinform..