PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways

MOTIVATION Availability of the sequences of entire genomes shifts the scientific curiosity towards the identification of function of the genomes in large scale as in genome studies. In the near future, data produced about cellular processes at molecular level will accumulate with an accelerating rate as a result of proteomics studies. In this regard, it is essential to develop tools for storing, integrating, accessing, and analyzing this data effectively. RESULTS We define an ontology for a comprehensive representation of cellular events. The ontology presented here enables integration of fragmented or incomplete pathway information and supports manipulation and incorporation of the stored data, as well as multiple levels of abstraction. Based on this ontology, we present the architecture of an integrated environment named Patika (Pathway Analysis Tool for Integration and Knowledge Acquisition). Patika is composed of a server-side, scalable, object-oriented database and client-side editors to provide an integrated, multi-user environment for visualizing and manipulating network of cellular events. This tool features automated pathway layout, functional computation support, advanced querying and a user-friendly graphical interface. We expect that Patika will be a valuable tool for rapid knowledge acquisition, microarray generated large-scale data interpretation, disease gene identification, and drug development. AVAILABILITY A prototype of Patika is available upon request from the authors.

[1]  R. Brent,et al.  Modelling cellular behaviour , 2001, Nature.

[2]  G. Rubin,et al.  The Role of the Genome Project in Determining Gene Function: Insights from Model Organisms , 1996, Cell.

[3]  James C. Schaff,et al.  The Virtual Cell , 1998, Pacific Symposium on Biocomputing.

[4]  Xin Chen,et al.  The TRANSFAC system on gene expression regulation , 2001, Nucleic Acids Res..

[5]  Toshihisa Takagi,et al.  Knowledge representation of signal transduction pathways , 2001, Bioinform..

[6]  Prasanna R. Kolatkar,et al.  BioJAKE: A Tool for the Creation, Visualization and Manipulation of Metabolic Pathways , 1998, Pacific Symposium on Biocomputing.

[7]  Masaru Tomita,et al.  E-CELL: software environment for whole-cell simulation , 1999, Bioinform..

[8]  G. Sermonti The human genome. , 1988, Rivista di biologia.

[9]  D. Lancet,et al.  GeneCards: integrating information about genes, proteins and diseases. , 1997, Trends in genetics : TIG.

[10]  Jack A. Orenstein,et al.  The ObjectStore database system , 1991, CACM.

[11]  Aviv Regev,et al.  Representation and Simulation of Biochemical Processes Using the pi-Calculus Process Algebra , 2000, Pacific Symposium on Biocomputing.

[12]  M. Vidal A Biological Atlas of Functional Maps , 2001, Cell.

[13]  Ugur Dogrusöz,et al.  Graph Visualization Toolkits , 2002, IEEE Computer Graphics and Applications.

[14]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[15]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence data bank and its supplement TrEMBL , 1997, Nucleic Acids Res..

[16]  Michael L. Mavrovouniotis,et al.  Petri Net Representations in Metabolic Pathways , 1993, ISMB.

[17]  A. Arkin,et al.  Stochastic mechanisms in gene expression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Ioannis Xenarios,et al.  DIP: the Database of Interacting Proteins , 2000, Nucleic Acids Res..

[19]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[20]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[21]  Peter Eades,et al.  A Heuristic for Graph Drawing , 1984 .

[22]  E. Davidson,et al.  The hardwiring of development: organization and function of genomic regulatory systems. , 1997, Development.

[23]  Ioannis Xenarios,et al.  DIP: The Database of Interacting Proteins: 2001 update , 2001, Nucleic Acids Res..

[24]  Isabel Rojas,et al.  A graph layout algorithm for drawing metabolic pathways , 2001, Bioinform..

[25]  Peter D. Karp,et al.  Automated Drawing of Metabolic Pathways , 2000 .

[26]  Tsuguchika Kaminuma,et al.  A Pathway Finding System for the Cell Signaling Networks Database , 1998, Silico Biol..

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

[28]  R Hofestädt,et al.  Quantitative modeling of biochemical networks , 1998, Silico Biol..