MoNetFamily: a web server to infer homologous modules and module–module interaction networks in vertebrates

A module is a fundamental unit forming with highly connected proteins and performs a certain kind of biological functions. Modules and module–module interaction (MMI) network are essential for understanding cellular processes and functions. The MoNetFamily web server can identify the modules, homologous modules (called module family) and MMI networks across multiple species for the query protein(s). This server first finds module candidates of the query by using BLASTP to search the module template database (1785 experimental and 1252 structural templates). MoNetFamily then infers the homologous modules of the selected module candidate using protein–protein interaction (PPI) families. According to homologous modules and PPIs, we statistically calculated MMIs and MMI networks across multiple species. For each module candidate, MoNetFamily identifies its neighboring modules and their MMIs in module networks of Homo sapiens, Mus musculus and Danio rerio. Finally, MoNetFamily shows the conserved proteins, PPI profiles and functional annotations of the module family. Our results indicate that the server can be useful for MMI network (e.g. 1818 modules and 9678 MMIs in H. sapiens) visualizations and query annotations using module families and neighboring modules. We believe that the server is able to provide valuable insights to determine homologous modules and MMI networks across multiple species for studying module evolution and cellular processes. The MoNetFamily sever is available at http://monetfamily.life.nctu.edu.tw.

[1]  R. Roeder,et al.  Dynamic regulation of pol II transcription by the mammalian Mediator complex. , 2005, Trends in biochemical sciences.

[2]  K. Garcia,et al.  Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. , 2003, Science.

[3]  M. Schwartz,et al.  Integrins and cell proliferation: regulation of cyclin-dependent kinases via cytoplasmic signaling pathways. , 2001, Journal of cell science.

[4]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[5]  Ginestra Bianconi,et al.  Scale-free networks with an exponent less than two. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[6]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[7]  Christian von Mering,et al.  STRING 8—a global view on proteins and their functional interactions in 630 organisms , 2008, Nucleic Acids Res..

[8]  J. Stankova,et al.  Janus Kinase 2 Activation by the Platelet-Activating Factor Receptor (PAFR): Roles of Tyk2 and PAFR C Terminus1 , 2003, The Journal of Immunology.

[9]  J. Justement,et al.  Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms , 1990, The Journal of experimental medicine.

[10]  D. Pe’er,et al.  Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data , 2003, Nature Genetics.

[11]  Tim J. P. Hubbard,et al.  SCOP database in 2004: refinements integrate structure and sequence family data , 2004, Nucleic Acids Res..

[12]  Livia Perfetto,et al.  MINT, the molecular interaction database: 2009 update , 2009, Nucleic Acids Res..

[13]  M. Gerstein,et al.  Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs. , 2004, Genome research.

[14]  A. Kallioniemi,et al.  MED29, a component of the mediator complex, possesses both oncogenic and tumor suppressive characteristics in pancreatic cancer , 2011, International journal of cancer.

[15]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[16]  H. Mewes,et al.  The FunCat, a functional annotation scheme for systematic classification of proteins from whole genomes. , 2004, Nucleic acids research.

[17]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..

[18]  X. Gu,et al.  Evolutionary Analysis for Functional Divergence of Jak Protein Kinase Domains and Tissue-Specific Genes , 2002, Journal of Molecular Evolution.

[19]  Maria Victoria Schneider,et al.  MINT: a Molecular INTeraction database. , 2002, FEBS letters.

[20]  Sourav Bandyopadhyay,et al.  Rewiring of Genetic Networks in Response to DNA Damage , 2010, Science.

[21]  Daphne Koller,et al.  A Complex-based Reconstruction of the Saccharomyces cerevisiae Interactome *S⃞ , 2009, Molecular & Cellular Proteomics.

[22]  Ingmar Reuter,et al.  Integr8 and Genome Reviews: integrated views of complete genomes and proteomes , 2004, Nucleic Acids Res..

[23]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[24]  Kai Xu,et al.  Visualization and analysis of the complexome network of Saccharomyces cerevisiae. , 2011, Journal of proteome research.

[25]  K. Garcia,et al.  Hexameric Structure and Assembly of the Interleukin-6/IL-6 α-Receptor/gp130 Complex , 2003, Science.

[26]  Gary D. Bader,et al.  Cytoscape Web: an interactive web-based network browser , 2010, Bioinform..

[27]  Chun-Yu Lin,et al.  PPISearch: a web server for searching homologous protein–protein interactions across multiple species , 2009, Nucleic Acids Res..

[28]  J. Fridman,et al.  Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. , 2011, The Journal of investigative dermatology.

[29]  Berend Snel,et al.  Quantifying modularity in the evolution of biomolecular systems. , 2004, Genome research.

[30]  Hans-Werner Mewes,et al.  CORUM: the comprehensive resource of mammalian protein complexes , 2007, Nucleic Acids Res..

[31]  James R Kiefer,et al.  Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6. , 2010, Journal of molecular biology.

[32]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of genome information in 2007 , 2007, Nucleic Acids Res..

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

[34]  Mei Sun,et al.  MED19 promotes proliferation and tumorigenesis of lung cancer , 2011, Molecular and Cellular Biochemistry.

[35]  D. Chan,et al.  Analysis of the Human Endogenous Coregulator Complexome , 2011, Cell.

[36]  R. Mesa.  Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis. , 2010, IDrugs : the investigational drugs journal.

[37]  Jinn-Moon Yang,et al.  3D-partner: a web server to infer interacting partners and binding models , 2007, Nucleic Acids Res..

[38]  P. Bork,et al.  Identification and analysis of evolutionarily cohesive functional modules in protein networks. , 2006, Genome research.

[39]  David Botstein,et al.  GO: : TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes , 2004, Bioinform..

[40]  James G. Krueger,et al.  Pathogenesis and therapy of psoriasis , 2007, Nature.

[41]  Chun-Yu Lin,et al.  PCFamily: a web server for searching homologous protein complexes , 2010, Nucleic Acids Res..

[42]  Joaquín Dopazo,et al.  Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling , 2010, Nucleic Acids Res..

[43]  Kara Dolinski,et al.  The BioGRID Interaction Database: 2011 update , 2010, Nucleic Acids Res..

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

[45]  R. Roeder,et al.  TRAP/SMCC/Mediator-Dependent Transcriptional Activation from DNA and Chromatin Templates by Orphan Nuclear Receptor Hepatocyte Nuclear Factor 4 , 2002, Molecular and Cellular Biology.