TY - JOUR A1 - Schmitt, William A. A1 - Raab, R. Michael A1 - Stephanopoulos, Gregory T1 - Elucidation of Gene Interaction Networks Through Time-Lagged Correlation Analysis of Transcriptional Data Y1 - 2004/08/01 JF - Genome Research JO - Genome Research SP - 1654 EP - 1663 DO - 10.1101/gr.2439804 VL - 14 IS - 8 UR - http://genome.cshlp.org/content/14/8/1654.abstract N2 - 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. ER -