Resources: GRNsight server for visualizing models of small- to medium-scale gene regulatory networks available

Kam Dahlquist • January 4, 2016

Resources: GRNsight server for visualizing models of small- to medium-scale gene regulatory networks available

The Loyola Marymount University Bioinformatics and Biomathematics groups are pleased to announce that GRNsight (http://dondi.github.io/GRNsight/), a web app and service for visualizing small- to medium-scale models of gene regulatory networks is available.

A gene regulatory network consists of genes, transcription factors, and the regulatory connections between them which govern the level of expression of mRNA and protein from genes. Our group has used a MATLAB program to perform parameter estimation and forward simulation of the dynamics of a differential equations model of a GRN with 21 nodes and 30 edges (Dahlquist, K. D., Fitzpatrick, B. G., Camacho, E. T., Entzminger, S. D., and Wanner, N. C. (2015) Parameter Estimation for Gene Regulatory Networks from Microarray Data: Cold Shock Response in Saccharomyces cerevisiae. Bulletin of Mathematical Biology, 77, 1457-1492. First published on September 29, 2015, 10.1007/s11538-015-0092-6, http://link.springer.com/article/10.1007/s11538-015-0092-6).

We wanted a quick and easy way to visualize the weight parameters from the model which represent the direction and magnitude of the influence of a transcription factor on its target gene, so we created GRNsight. GRNsight automatically lays out either an unweighted or weighted network graph based on an Excel input spreadsheet containing an adjacency matrix where regulators are named in the columns and target genes in the rows. For an unweighted network, each cell in the matrix should contain a "zero" if there is no regulatory relationship between the regulator and target, or a "one" if there is a regulatory relationship between them. In a weighted network, the "one's" are replaced with a real number that is the weight parameter.

When a user uploads a spreadsheet with an unweighted adjacency matrix, GRNsight automatically lays out the graph using black lines and pointed arrowheads. When a user uploads a spreadsheet with a weighted adjacency matrix, GRNsight uses pointed and blunt arrowheads, and colors the edges and adjusts their thicknesses based on the sign (positive for activation or negative for repression) and magnitude of the weight parameter.

GRNsight is written in JavaScript, with diagrams facilitated by D3.js, a data visualization library. Node.js and the Express framework handle server-side functions. GRNsight's diagrams are based on D3.js's force graph layout algorithm, which was then extensively customized to support the specific needs of GRN visualization. Nodes are rectangular and support gene labels of up to 12 characters. The edges are arcs, which become straight lines when the nodes are close together. Self-regulatory edges are indicated by a loop on the lower-right side of a node. When a user mouses over an edge, the numerical value of the weight parameter is displayed. Visualizations can be modified through manual node dragging and sliders that adjust D3.js's force layout parameters.

GRNsight is best-suited for visualizing networks of fewer than 35 nodes and 70 edges, although it will accept networks of up to 75 nodes and 150 edges. GRNsight has a demo function that allows users to load sample data from Dahlquist et al. (2015). Although it was originally designed to facilitate visualization of these demo data, we believe that GRNsight has general utility for the systems biology community as a simple and quick way to view data in an adjacency matrix format.

Formatting instructions and links to download the sample Excel spreadsheets can be found on the Documentation page of the web site (http://dondi.github.io/GRNsight/documentation.html), which also includes instructions on how the user can manipulate and interpret the display.

Every user's submitted data are private and not viewable by anyone other than the user. Uploaded data reside as temporary files and are deleted from the GRNsight server during standard operating system file cleanup procedures. GRNsight follows an open development model with rigorous documentation of requirements and issues on GitHub (https://github.com/dondi/GRNsight).

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