PAGE is a Java-based software for phase-shifted analysis of gene expression developed along the lines of the original q-Clustering algorithm (Ji and Tan, 2005) to analyze gene expression from multiple biological conditions across dose and time series experiments. Grouping of gene expression patterns is performed in q-intervals of the measurements using phase-shifts to find clusters of genes which share trends of expression profiles within the dataset. The PAGE method has three phases:
Phase 1: Gene expression pattern matrix transformation into -1,0,1 to indicate the direction of expression change from each biological condition at fixed time and dose points. All biological replicates are averaged if provided.
Phase 2: Generate q-clusters which have similar patterns of expression of over q-consecutive conditions
Phase 3: Assign a significance score for each bicluster in all q-Clusters and identify the inhibition patterns of each q-Cluster.
Window size and threshold parameters are used in PAGE to specify the q-interval consecutive points and the slope cut-off for defining the upward and downward trends respectively. The patterns and genes within the q-Clusters are visualized in trend plots and also compared to determine biological relevance from the gene annotations.
PAGE is an interactive tool that uses a line graph to dynamically illustrate the phase-shifted patterns of gene expressions based on the q-Cluster selected by the users. Each line shown on the line graph represents the trend of a bicluster whose score is equal to or below the maximum threshold value. The line graph is capable of zooming and can be exported in jpg format. Also, the genes associated with the trends shown on line graph can be exported to a text file for other analysis. Furthermore, all phase-shifted patterns in each of the q-Clusters can be exported as a tab-delimited text file, which can be readily imported to other spreadsheet applications.
Requirements for PAGE
The gene expression data needs to be normalized and transformed to the user's satisfaction. In addition, missing data needs to be imputed and all dose and time points need to be consecutive with at least one interval (two adjacent points). Finally, the software has been tested to run on Windows PCs running the XP operating system and requires JRE version 1.4.2 or later.
Public Domain Notice
This is U.S. government work. Under 17 U.S.C. 105 no copyright is claimed and it may be freely distributed and copied.
Pierre R. Bushel, Ph.D.