Pathway Projector: Web-Based Zoomable Pathway Browser Using KEGG Atlas and Google Maps API

Background Biochemical pathways provide an essential context for understanding comprehensive experimental data and the systematic workings of a cell. Therefore, the availability of online pathway browsers will facilitate post-genomic research, just as genome browsers have contributed to genomics. Many pathway maps have been provided online as part of public pathway databases. Most of these maps, however, function as the gateway interface to a specific database, and the comprehensiveness of their represented entities, data mapping capabilities, and user interfaces are not always sufficient for generic usage. Methodology/Principal Findings We have identified five central requirements for a pathway browser: (1) availability of large integrated maps showing genes, enzymes, and metabolites; (2) comprehensive search features and data access; (3) data mapping for transcriptomic, proteomic, and metabolomic experiments, as well as the ability to edit and annotate pathway maps; (4) easy exchange of pathway data; and (5) intuitive user experience without the requirement for installation and regular maintenance. According to these requirements, we have evaluated existing pathway databases and tools and implemented a web-based pathway browser named Pathway Projector as a solution. Conclusions/Significance Pathway Projector provides integrated pathway maps that are based upon the KEGG Atlas, with the addition of nodes for genes and enzymes, and is implemented as a scalable, zoomable map utilizing the Google Maps API. Users can search pathway-related data using keywords, molecular weights, nucleotide sequences, and amino acid sequences, or as possible routes between compounds. In addition, experimental data from transcriptomic, proteomic, and metabolomic analyses can be readily mapped. Pathway Projector is freely available for academic users at http://www.g-language.org/PathwayProjector/.

[1]  Kenneth E. Rudd,et al.  EcoGene: a genome sequence database for Escherichia coli K-12 , 2000, Nucleic Acids Res..

[2]  S. Lewis,et al.  The generic genome browser: a building block for a model organism system database. , 2002, Genome research.

[3]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[4]  Masaru Tomita,et al.  G-language Genome Analysis Environment: a workbench for nucleotide sequence data mining , 2003, Bioinform..

[5]  Jason A. Papin,et al.  Metabolic pathways in the post-genome era. , 2003, Trends in biochemical sciences.

[6]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[7]  Sarah M. Keating,et al.  Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project. , 2004, Systems biology.

[8]  Rolf Apweiler,et al.  IntEnz, the integrated relational enzyme database , 2004, Nucleic Acids Res..

[9]  Carol Friedman,et al.  Information Visualization Techniques in Bioinformatics during the Postgenomic Era. , 2004, Drug discovery today. Biosilico.

[10]  Hubert Hackl,et al.  PathwayExplorer: web service for visualizing high-throughput expression data on biological pathways , 2005, Nucleic Acids Res..

[11]  Cathy H. Wu,et al.  The Universal Protein Resource (UniProt) , 2005, Nucleic Acids Res..

[12]  Jihoon Kim,et al.  ArrayXPath II: mapping and visualizing microarray gene-expression data with biomedical ontologies and integrated biological pathway resources using Scalable Vector Graphics , 2005, Nucleic Acids Res..

[13]  Masaru Tomita,et al.  KEGG-Based Pathway Visualization Tool for Complex Omics Data , 2005, Silico Biol..

[14]  Falk Schreiber,et al.  VANTED: A system for advanced data analysis and visualization in the context of biological networks , 2006, BMC Bioinformatics.

[15]  C. Ouzounis,et al.  Expansion of the BioCyc collection of pathway/genome databases to 160 genomes , 2005, Nucleic acids research.

[16]  Masaru Tomita,et al.  GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes , 2006, BMC Bioinformatics.

[17]  Carole A. Goble,et al.  Taverna: a tool for building and running workflows of services , 2006, Nucleic Acids Res..

[18]  Alexander R. Pico,et al.  GenMAPP 2: new features and resources for pathway analysis , 2007, BMC Bioinformatics.

[19]  Dinanath Sulakhe,et al.  PUMA2—grid-based high-throughput analysis of genomes and metabolic pathways , 2005, Nucleic Acids Res..

[20]  Dimitris Dimitropoulos,et al.  Using MSDchem to search the PDB ligand dictionary. , 2006, Current protocols in bioinformatics.

[21]  Suzanne M. Paley,et al.  The Pathway Tools cellular overview diagram and Omics Viewer , 2006, Nucleic acids research.

[22]  Masaru Tomita,et al.  MEGU: Pathway Mapping Web-Service Based on KEGG and SVG , 2006, Silico Biol..

[23]  Ikuo Uchiyama,et al.  CGAT: a comparative genome analysis tool for visualizing alignments in the analysis of complex evolutionary changes between closely related genomes , 2006, BMC Bioinformatics.

[24]  Masaru Tomita,et al.  G-language System as a platform for large-scale analysis of high-throughput omics data , 2006 .

[25]  Sean Ekins,et al.  Pathway mapping tools for analysis of high content data. , 2007, Methods in molecular biology.

[26]  Wolfgang Wurst,et al.  A New Partner for the International Knockout Mouse Consortium , 2007, Cell.

[27]  Wolfgang Wurst,et al.  A Mouse for All Reasons , 2007, Cell.

[28]  Alexander R. Pico,et al.  WikiPathways: Pathway Editing for the People , 2008, PLoS biology.

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

[30]  Judith A. Blake,et al.  The Mouse Genome Database (MGD): mouse biology and model systems , 2007, Nucleic Acids Res..

[31]  Kara Dolinski,et al.  Gene Ontology annotations at SGD: new data sources and annotation methods , 2007, Nucleic Acids Res..

[32]  T. Werner Bioinformatics applications for pathway analysis of microarray data. , 2008, Current opinion in biotechnology.

[33]  Donna Karolchik,et al.  UCSC genome browser: deep support for molecular biomedical research. , 2008, Biotechnology annual review.

[34]  Masaru Tomita,et al.  Computational Genome Analysis Using The G-language System , 2008 .

[35]  Alexander R. Pico,et al.  The public road to high-quality curated biological pathways. , 2008, Drug discovery today.

[36]  P. Bork,et al.  iPath: interactive exploration of biochemical pathways and networks. , 2008, Trends in biochemical sciences.

[37]  Masaru Tomita,et al.  Genome Projector: zoomable genome map with multiple views , 2009, BMC Bioinformatics.

[38]  Gultekin Özsoyoglu,et al.  PathCase: pathways database system , 2008, Bioinform..

[39]  Peer Bork,et al.  KEGG Atlas mapping for global analysis of metabolic pathways , 2008, Nucleic Acids Res..

[40]  Michael Darsow,et al.  ChEBI: a database and ontology for chemical entities of biological interest , 2007, Nucleic Acids Res..

[41]  Kei-Hoi Cheung,et al.  Bringing Web 2.0 to bioinformatics , 2008, Briefings Bioinform..

[42]  Masumi Itoh,et al.  CGAS: comparative genomic analysis server , 2009, Bioinform..

[43]  Shuhong Zhao,et al.  Understanding Quantitative Genetics in the Systems Biology Era , 2009, International journal of biological sciences.

[44]  Torsten Schwede,et al.  The SWISS-MODEL Repository and associated resources , 2008, Nucleic Acids Res..

[45]  Ting Wang,et al.  The UCSC Genome Browser Database: update 2009 , 2008, Nucleic Acids Res..

[46]  Kengo Kinoshita,et al.  ATTED-II provides coexpressed gene networks for Arabidopsis , 2008, Nucleic Acids Res..

[47]  Antje Chang,et al.  BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009 , 2008, Nucleic Acids Res..

[48]  The UniProt Consortium,et al.  The Universal Protein Resource (UniProt) 2009 , 2008, Nucleic Acids Res..

[49]  Andrew M. Jenkinson,et al.  Ensembl 2009 , 2008, Nucleic Acids Res..

[50]  Andrew G. McDonald,et al.  ExplorEnz: the primary source of the IUBMB enzyme list , 2008, Nucleic Acids Res..

[51]  Peter D. Karp,et al.  EcoCyc: A comprehensive view of Escherichia coli biology , 2008, Nucleic Acids Res..

[52]  Lincoln Stein,et al.  Reactome knowledgebase of human biological pathways and processes , 2008, Nucleic Acids Res..