INTEGRATOR: interactive graphical search of large protein interactomes over the Web

Abstract

Background: The rapid growth of protein interactome data has elevated the necessity and importance of network analysis tools. However, unlike pure text data, network search spaces are of exponential complexity. This poses special challenges for storing, searching, and navigating this data efficiently. Moreover, development of effective web interfaces has been difficult.

Results: We present Integrator, a web-integrated graphical search tool for protein-protein interaction networks across 50+ genomes.

Conclusion: Integrator provides single and multiple protein searches of the Bioverse database containing experimentally-derived and predicted protein-protein interactions. The interface provides animated local network views, rapid subgraph manipulation, and cross-referencing of functional annotations. Integrator is available at http://bioverse.compbio.washington.edu/integrator.

Figure 1

Frame-by-frame network navigation. A search begins at node 1 in the left-most window. Once node 2 is reached in the middle window, a new search is performed to center the network around that node. This process is repeated at node 3 in the right-most window. A connected network can be fully traversed using this method. This localized navigation approach works well to reconcile the exponential complexity of networks and the limitations of two-dimensional viewers.

Figure 2

The Integrator network viewer interface. Shown here is a representative network search result around a selected node (yellow) with various other nodes modified for color, size, or shape. The center frame contains the main interactive graph viewer. Users can traverse a network by clicking on nodes. Double-clicking on a node opens a window containing detailed sequence and annotation information. Hovering over nodes also brings up tool tips containing GO and Interpro annotations. Hovering over edges shows tool tips with edge confidence data. Right-click contextual menus also exist for nodes and edges which allow for search, hiding, showing, and changing their visual properties. The slider bar at the top of the graph viewer modulates zoom, rotation, or viewable neighborhood size. Below this are two interactive network tables, nodes on the left, edges on the right. These tables can be used to sort and modify various node and edge properties in the viewer.

Figure 3

Multiple protein identifier search results. A representative search result where three clusters (defined by connected graph components) are shown with their constituent nodes. Each of the individual clusters can be viewed graphically by following their hyperlinks.

Figure 4

Comparison of a graph-only viewer versus the graph-plus-table interface as provided by Integrator. (A) Network viewer without a table interface, previously released by our group (). Subgraph operations are performed one node or edge at a time. (B) Integrator network before subgraphing. (C) Integrator network after subgraphing. Subgraphs can be specified on any number of node or edge properties just by sorting columns and selecting the desired rows.