@article{Schmitt01082004, author = {Schmitt, William A. and Raab, R. Michael and Stephanopoulos, Gregory}, title = {Elucidation of Gene Interaction Networks Through Time-Lagged Correlation Analysis of Transcriptional Data}, volume = {14}, number = {8}, pages = {1654-1663}, year = {2004}, doi = {10.1101/gr.2439804}, abstract ={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.}, URL = {http://genome.cshlp.org/content/14/8/1654.abstract}, eprint = {http://genome.cshlp.org/content/14/8/1654.full.pdf+html}, journal = {Genome Research} }