KEGG is the most comprehensive pathway database and these maps are used extensively in biological research. KEGG has grown, many new features have been incorporated. However, in Cytoscape the support for KEGG is very primitive (Figure1). So we implemented KGML (KEGG Markup Language) import plugin named KGMLReader (Figure2). This plugin currently supports all metabolic kgml. In this poster we show the features, VizMap examples, and future plans of this plugin.

KEGG pathway import using KGMLKGMLreader supports all metabolic pathways (Figure2) which include KEGG new pathway called global metabolism map. This global map is useful to compare the entire metabolism in different organism (Figure3-5) or conditions such as dynamical changes of gene expression in a time-series microarray experiment (Figure6).

1. Okuda S, Yamada T, et al. (2008) KEGG Atlas mapping for global analysis of metabolic pathways: Nucleic Acids Res 1; 36.2. Katayama T, Nakao M, et al. (2010) TogoWS integrated SOAP and REST APIs for interoperable bioinformatics Web services: Nucleic Acids Res 1; 38.

In Cytoscape the support for KEGG is very primitive, there are still remaining issues such as:

•Importing all KEGG pathways with same biological layout•VizMap optimized for the imported pathway•Supplementing information for the imported pathway•Navigation optimized for the imported pathway

To solve these issues we added following functions to Cytoscape:

•Network import using KGML (XML)•Custom node graphics VizMap using Google Chart APIAttribute supplement using TogoWS REST service

Chart image mapping by Google Chart APIIn coming Cytoscape 2.8 users can VizMap expression chart on the enzyme node using Google Chart API. This pathway is VizMapped time-series expression. Red and blue lines are gene expression profiles (Red=MT, Blue=WT). The background color orange and blue means significantly over or under-expressed in mutant than WT in KEGG module (Pval < 0.05).

Annotation import from TogoWSKGML includes the component entry_id and short name, but doesn’t include id-link to other database and useful other KEGG metadata. To retrieve such data as network attribute, we utilized TogoWS REST service. This service enables KEGG entry field extraction by requesting these simple URLs (Figure8).

Abstract Features Future plans

References

Objectives

Kozo Nishida / Keiichiro OnoNara institute of science and technology / University of California, San Diego

KEGG pathway support in Cytoscape and data mapping by custom graphics

Figure1. network using old KEGG biopax

Figure2. network using KGML

Figure3. Global metabolism map (Ecoli) Figure4. Global metabolism map (Yeast)

Figure5. Global metabolism map (human)Figure6. Time-series transition of Global metabolism map VizMapped differentially expressed pathway

time1

time2

time3

time4

time5

time6

Red=over-expressed in MT thanWT (Pval < 0.05), Green=under-expressed

Figure7. Pathway VizMapped time-series expression profile using Google Chart API Figure8. Network attribute set by requesting TogoWS REST URL

Maplink node navigation using Nested Network Format(NNF)From Cytoscape 2.7 users can embed network into a node. We will implement user selected pathway expansion and improve visualization of differentially expressed pathways.

expand NNFselected differentially expressed pathways

Figure9. Maplink node expansion and merging differentially expressed pathways

Merge using maplink node

One global differentially expressed pathway

Custom pathway search user interfaceManual change of VizMap for many KEGG attributes is troublesome. So we will add a KEGG specialized search and selection input box.

Filtering items:•pathway category•KEGG module

Floating information window for a pathwayWe will add floating window for diversities of gene expression and reaction node’s centrality in each pathway using boxplot.

Other future plansdata integration using other API•bridgedb•MASSBANK

extension using Processing visualizer•multi layered network•3D visualization•animation

cooperation with other plugins•Webservice client plugin•CyAnimator•Advance network merge

KGMLReader project web site: http://code.google.com/p/kgmlreader

Figure10. KEGG specialized search and selection images

Figure11. Floating window for a pathway info