Elucidation of gene interaction networks through time-lagged correlation analysis of transcriptional data

• Published in: Genome research 2004-08, Vol.14 (8), p.1654-1663
• Main Authors: Schmitt, Jr, William A, Raab, R Michael, Stephanopoulos, Gregory
• Format: Article
• Language: English
• Subjects: Cyanobacteria - genetics; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genome, Bacterial; Light; Methods; Models, Biological; Oligonucleotide Array Sequence Analysis - methods; Time Factors
• ISSN: 1088-9051
• DOI: 10.1101/gr.2439804

The photosynthetic cyanobacterium Synechocystis sp. strain PCC 6803 uses a complex genetic program to control its physiological response to alternating light conditions. To study this regulatory program time-series experiments were conducted by exposing Synechocystis sp. to serial perturbations in light intensity. In each experiment whole-genome DNA microarrays were used to monitor gene transcription in 20-min intervals over 8- and 16-h periods. The data was analyzed using time-lagged correlation analysis, which identifies genetic interaction networks by constructing correlations between time-shifted transcription profiles with different levels of statistical confidence. These networks allow inference of putative cause-effect relationships among the organism's genes. Using light intensity as our initial input signal, we identified six groups of genes whose time-lagged profiles possessed significant correlation, or anti-correlation, with the light intensity. We expanded this network by using the average profile from each group of genes as a seed, and searching for other genes whose time-lagged profiles possessed significant correlation, or anti-correlation, with the group's average profile. The final network comprised 50 different groups containing 259 genes. Several of these gene groups possess known light-stimulated gene clusters, such as Synechocystis sp. photosystems I and II and carbon dioxide fixation pathways, while others represent novel findings in this work.