VisANT 3.0: new modules for pathway visualization, editing, prediction and construction

Abstract

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu.

Figure 1.

Illustration of multi-scale visualization of pathways using VisANT's metagraph capability. Green boxes are contracted metanodes representing a group of enzymes that catalyze a common reaction; filled green circles represent enzymes and open circles represent compounds. (A) KEGG Yeast pathways shown in VisANT by first loading MAP00220 and then expanding MAP00910. The connection between MAP00910 and MAP00251 is shown only after MAP00910 is expanded. (B) The eight pathways are all represented as contracted linked metanodes. A and B can be alternately displayed by toggling the state of the metanodes.

Figure 2.

Different methods of loading pathways into VisANT. (A) KEGG pathways for a given species can be directly browsed and pathways of interest can be loaded by clicking the ‘graphics’ link. A pathway can also be located and loaded by using its (B) name or ID, (C) a URL or (D) KGML contents copied/pasted into the ‘Add’ box. (E) Pathway IDs will be shown in a node's tooltip if the protein/gene is involved in one or more pathways. In such a case, a pathway can be directly loaded using a set of drop down menus as shown above.

Figure 3.

Illustration of pathway enrichment. (A) H. sapiens notch signaling pathway, the γ-secretase complex is represented as nested metanodes. Five components are shown in the complex. (B) VisANT plugin for the GeneRecommender service searches for the top 10 coexpressed genes with a given set of query genes shown in the left panel. Score plotter of the top 10 coexpressed genes is shown in the right panel. (C) Expression data of the top 50 experiments, as well as additional genes excluding the query set, are returned and integrated with the existing network. New genes are shown using the circle layout. Expression of PSENEN is shown as an embedded plotter. Color is used to represent expression for the rest nine other genes with red for low expression values and green for high values. Gray is used to indicate that the expression value of the gene for the current experiment is missing. (D) The metanode of the γ-secretase complex is contracted and the expression plotter is turned on. All expression profiles for the member components are plotted together; the average profile is shown in black. The discontinuity is due to missing values for some components of corresponding experiments. (E) Querying against the Predictome database indicates that APH1A and PSENEN are functionally related (36).