CellCircuits: a database of protein network models

CellCircuits () is an open-access database of molecular network models, designed to bridge the gap between databases of individual pairwise molecular interactions and databases of validated pathways. CellCircuits captures the output from an increasing number of approaches that screen molecular interaction networks to identify functional subnetworks, based on their correspondence with expression or phenotypic data, their internal structure or their conservation across species. This initial release catalogs 2019 computationally derived models drawn from 11 journal articles and spanning five organisms (yeast, worm, fly, Plasmodium falciparum and human). Models are available either as images or in machine-readable formats and can be queried by the names of proteins they contain or by their enriched biological functions. We envision CellCircuits as a clearinghouse in which theorists may distribute or revise models in need of validation and experimentalists may search for models or specific hypotheses relevant to their interests. We demonstrate how such a repository of network models is a novel systems biology resource by performing several meta-analyses not currently possible with existing databases.

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

[2]  Jacky L. Snoep,et al.  BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems , 2005, Nucleic Acids Res..

[3]  Peter D. Karp,et al.  MetaCyc: a multiorganism database of metabolic pathways and enzymes , 2005, Nucleic Acids Res..

[4]  Marc Vidal,et al.  Interactome modeling , 2005, FEBS letters.

[5]  P. Bork,et al.  Dynamic Complex Formation During the Yeast Cell Cycle , 2005, Science.

[6]  P. Karp.  Call for an enzyme genomics initiative , 2004, Genome Biology.

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

[8]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of proteins from whole genomes in 2005 , 2005, Nucleic Acids Res..

[9]  A. Valencia,et al.  Text-mining and information-retrieval services for molecular biology , 2005, Genome Biology.

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

[11]  N. Gough,et al.  Mapping Cellular Signaling , 2002, Science's STKE.

[12]  Imre Vastrik,et al.  Reactome: a knowledgebase of biological pathways , 2004, OTM Workshops.

[13]  William Feller,et al.  An Introduction to Probability Theory and Its Applications , 1951 .

[14]  Gabriele Ausiello,et al.  MINT: the Molecular INTeraction database , 2006, Nucleic Acids Res..

[15]  Nevan J Krogan,et al.  Systems-level analyses identify extensive coupling among gene expression machines , 2006, Molecular systems biology.

[16]  Trey Ideker,et al.  Damage recovery pathways in Saccharomyces cerevisiae revealed by genomic phenotyping and interactome mapping. , 2002, Molecular cancer research : MCR.

[17]  Rafael A Irizarry,et al.  Global synthetic-lethality analysis and yeast functional profiling. , 2006, Trends in genetics : TIG.

[18]  J. Rothberg,et al.  Gaining confidence in high-throughput protein interaction networks , 2004, Nature Biotechnology.

[19]  Mike Tyers,et al.  BioGRID: a general repository for interaction datasets , 2005, Nucleic Acids Res..

[20]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[21]  Gene Ontology Consortium.  The Gene Ontology (GO) database and informatics resource , 2003 .

[22]  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..

[23]  Ian M. Donaldson,et al.  BIND: the Biomolecular Interaction Network Database , 2001, Nucleic Acids Res..

[24]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

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

[26]  Richard J Roberts,et al.  Identifying Protein Function—A Call for Community Action , 2004, PLoS biology.

[27]  Alexander J. Hartemink,et al.  Informative Structure Priors: Joint Learning of Dynamic Regulatory Networks from Multiple Types of Data , 2004, Pacific Symposium on Biocomputing.

[28]  B. Snel,et al.  Comparative assessment of large-scale data sets of protein–protein interactions , 2002, Nature.

[29]  Joshua M. Stuart,et al.  A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules , 2003, Science.

[30]  T. Ideker,et al.  Integrating phenotypic and expression profiles to map arsenic-response networks , 2004, Genome Biology.

[31]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[32]  Tommi S. Jaakkola,et al.  Combining Location and Expression Data for Principled Discovery of Genetic Regulatory Network Models , 2001, Pacific Symposium on Biocomputing.

[33]  T. Ideker,et al.  Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae , 2006, Journal of biology.

[34]  W. Feller,et al.  An Introduction to Probability Theory and Its Application. , 1951 .

[35]  M. Vidal,et al.  Interactome: gateway into systems biology. , 2005, Human molecular genetics.

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

[37]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of proteins from whole genomes in 2005 , 2006, Nucleic Acids Res..

[38]  B. Palsson,et al.  The model organism as a system: integrating 'omics' data sets , 2006, Nature Reviews Molecular Cell Biology.

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

[40]  K. N. Chandrika,et al.  Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets , 2006, Nature Genetics.

[41]  Lincoln Stein,et al.  Reactome: a knowledgebase of biological pathways , 2004, Nucleic Acids Res..

[42]  T. Jaakkola,et al.  Validation and refinement of gene-regulatory pathways on a network of physical interactions , 2005, Genome Biology.

[43]  M. Gerstein,et al.  A Bayesian Networks Approach for Predicting Protein-Protein Interactions from Genomic Data , 2003, Science.

[44]  Nikolay A. Kolchanov,et al.  GeneNet in 2005 , 2004, Nucleic Acids Res..

[45]  Martin Vingron,et al.  IntAct: an open source molecular interaction database , 2004, Nucleic Acids Res..

[46]  Alexander E. Kel,et al.  TRANSPATH®: an information resource for storing and visualizing signaling pathways and their pathological aberrations , 2005, Nucleic Acids Res..

[47]  T. Sittler,et al.  The Plasmodium protein network diverges from those of other eukaryotes , 2005, Nature.

[48]  T. Ideker,et al.  Systematic interpretation of genetic interactions using protein networks , 2005, Nature Biotechnology.

[49]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[50]  Gary D. Bader,et al.  BioPAX - Biological Pathways Exchange Language Level 2, Version 1.0 Documentation , 2005 .

[51]  Benno Schwikowski,et al.  Discovering regulatory and signalling circuits in molecular interaction networks , 2002, ISMB.

[52]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.