TY - GEN
T1 - Fusion of domain knowledge for dynamic learning in transcriptional networks
AU - Harari, Oscar
AU - Romero-Zaliz, R.
AU - Rubio-Escudero, C.
AU - Zwir, I.
PY - 2006
Y1 - 2006
N2 - A critical challenge of the postgenomic era is to understand how genes are differentially regulated even when they belong to a given network. Because the fundamental mechanism controlling gene expression operates at the level of transcription initiation, computational techniques have been developed that identify cis-regulatory features and map such features into differential expression patterns. The fact that such co-regulated genes may be differentially regulated suggests that subtle differences in the shared cis-acting regulatory elements are likely significant. Thus, we carry out an exhaustive description of m-acting regulatory features including the orientation, location and number of binding sites for a regulatory protein, the presence of binding site submotifs, the class and number of RNA polymerase sites, as well as gene expression data, which is treated as one feature among many. These features, derived from different domain sources, are analyzed concurrently, and dynamic relations are recognized to generate profiles, which are groups of promoters sharing common features. We apply this method to probe the regulatory networks governed by the PhoP/PhoQ two-component system in the enteric bacteria Escherichia coli and Salmonella enterica. Our analysis uncovered novel members of the PhoP regulon as and the resulting profiles group genes that share underlying biological that characterize the system kinetics. The predictions were experimentally validated to establish that the PhoP protein uses multiple mechanisms to control gene transcription and is a central element in a highly connected network.
AB - A critical challenge of the postgenomic era is to understand how genes are differentially regulated even when they belong to a given network. Because the fundamental mechanism controlling gene expression operates at the level of transcription initiation, computational techniques have been developed that identify cis-regulatory features and map such features into differential expression patterns. The fact that such co-regulated genes may be differentially regulated suggests that subtle differences in the shared cis-acting regulatory elements are likely significant. Thus, we carry out an exhaustive description of m-acting regulatory features including the orientation, location and number of binding sites for a regulatory protein, the presence of binding site submotifs, the class and number of RNA polymerase sites, as well as gene expression data, which is treated as one feature among many. These features, derived from different domain sources, are analyzed concurrently, and dynamic relations are recognized to generate profiles, which are groups of promoters sharing common features. We apply this method to probe the regulatory networks governed by the PhoP/PhoQ two-component system in the enteric bacteria Escherichia coli and Salmonella enterica. Our analysis uncovered novel members of the PhoP regulon as and the resulting profiles group genes that share underlying biological that characterize the system kinetics. The predictions were experimentally validated to establish that the PhoP protein uses multiple mechanisms to control gene transcription and is a central element in a highly connected network.
UR - http://www.scopus.com/inward/record.url?scp=33750564964&partnerID=8YFLogxK
U2 - 10.1007/11875581_127
DO - 10.1007/11875581_127
M3 - Conference contribution
AN - SCOPUS:33750564964
SN - 3540454853
SN - 9783540454854
T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
SP - 1067
EP - 1078
BT - Intelligent Data Engineering and Automated Learning, IDEAL 2006 - 7th International Conference, Proceedings
PB - Springer Verlag
T2 - 7th International Conference on Intelligent Data Engineering and Automated Learning, IDEAL 2006
Y2 - 20 September 2006 through 23 September 2006
ER -