Category Cross-Omics>Pathway Analysis/ Gene Regulatory Networks/Tools

Abstract Cerebral (Cell Region-Based Rendering And Layout) is an open-source Java plug-in for the Cytoscape - (see G6G Abstract Number 20092) biomolecular interaction viewer.

Given an interaction network and subcellular localization annotation, Cerebral automatically generates a view of the network in the style of traditional ‘pathway diagrams’, providing an intuitive interface for the exploration of a biological pathway or system.

The molecules are separated into layers according to their subcellular localization. Potential products or outcomes of the pathway can be shown at the bottom of the view, clustered according to any molecular attribute data -- protein function -- for example.

Cerebral scales well to networks containing thousands of nodes.

Cerebral is a plug-in that enhances Cytoscape's functionality by using extra annotation provided by the user to both automatically generate a more pathway-like representation of a network and to provide an environment for the visualization, comparison, and clustering of expression data from multiple conditions.

Cerebral uses subcellular localization annotation (see below...) to create a layered view of a cell, placing nodes in the region of the screen corresponding to the appropriate localization.

Cerebral can also place a subset of nodes, regulated genes for example, at the bottom of the screen (as stated above…) and can further group these bottom most nodes according to any ‘user-specified attribute’.

Small multiple views enable a user to see expression data from two (2) or more conditions overlaid on a network, while a difference view allows two (2) conditions to be selected and a new view is colored based on the changes between the selected conditions.

An interactive ‘k-means clustering’ tool also allows users to cluster their data, using a slider to adjust the number of desired clusters, and quickly select nodes based on cluster membership.

While Cerebral was designed with ‘biological pathways’ in mind, it can also be used to lay out any graph that requires stratification according to some characteristic and thus can be used by researchers in a variety of fields, including the social sciences.

Cerebral subcellular localization annotation --

Cerebral can be used on any network for which subcellular localization annotation exists.

Localization information can be gathered from a number of resources, including databases such as Human Protein Reference Database (HPRD) or prediction methods such as PSORTb for bacteria or Proteome Analyst (PA) for eukaryotes.

Localization annotation does Not need to be complete, as reasonable results can be achieved with coverage as low as 30%. Nodes without annotated localization sites are positioned according to the location of their first neighbors.

Interacting (see below…) with a ‘large network’ is facilitated by panning and zooming, ‘intelligent labeling’ at multiple zoom levels, highlighting a node's first neighbors upon mouse over, category-based highlighting, automatic navigation that frames node neighbors in the view, and the grouping of edges into bundles to reduce clutter.

Cerebral Layout --

The manufacturer's ‘network layout algorithm’ was modeled after hand- drawn ‘pathway diagrams’. Nodes are restricted to a regular lattice grid which provides room for labels and eliminates overlapping nodes.

From an initial, random layout of nodes on the grid, neighboring layouts are stochastically sampled and evaluated until the layout stops improving. A neighboring layout is generated by moving a node to a new position within its subcellular compartment.

A position is evaluated by measuring: edge-edge and node-edge overlaps, the distance between nodes with similar molecular function, the distance between topological neighbors, and the empty space between unrelated nodes.

The efficiency of evaluation functions has previously been limited by the expense of scoring node-edge and edge-edge overlaps.

The manufacturers use a modified version of Bresenham's line drawing algorithm to increase efficiency by two (2) orders of magnitude.

Once the layout has been computed, the edges of high degree nodes are curved into bundles to reduce visual complexity. A light blue convex hull is also drawn around ‘pathway products’ that share molecular function.

Cerebral Interaction --

With a small network, Cerebral produces a sufficiently organized layout to be understood as a static diagram. For large networks, the inherent complexity requires ‘interaction techniques’ to understand the interactions.

Passing the mouse over a node of interest highlights its ‘first neighbors’ in red and brings the labels to the foreground. As nodes of interest are found, they can be assigned to groups with a simple right- click.

All members of the group can later be recalled and selected by ‘clicking on’ the group name in the plug-in's information panel. Node labels remain legible at different zoom levels and do Not overlap.

Edges are drawn on top of the nodes where they start and end, but drawn underneath any other node that they cross.

Finally, Cerebral has several navigation helpers allowing the user to ‘frame the view’ around nodes of interest.

Cerebral v.2.0 --

In this updated version of Cerebral, compatible with the Cytoscape 2.6.0 release, the manufacturers introduce their new ‘multi-experiment comparison’ tool.

With this new functionality, users can now upload, compare, contrast and cluster quantitative data from ‘multiple experiments’.

System Requirements

Contact manufacturer.


Manufacturer Web Site Cerebral

Price Cerebral is freely available under the BSD license.

G6G Abstract Number 20545

G6G Manufacturer Number 104160