This article is part of the supplement: The ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (IJCBS)
Robust inference of the context specific structure and temporal dynamics of gene regulatory network
1 Department of ECE, University of Texas at San Antonio, San Antonio, TX, USA
2 Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
3 Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
4 Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
BMC Genomics 2010, 11(Suppl 3):S11 doi:10.1186/1471-2164-11-S3-S11Published: 1 December 2010
Response of cells to changing endogenous or exogenous conditions is governed by intricate molecular interactions, or regulatory networks. To lead to appropriate responses, regulatory network should be 1) context-specific, i.e., its constituents and topology depend on the phonotypical and experimental context including tissue types and cell conditions, such as damage, stress, macroenvironments of cell, etc. and 2) time varying, i.e., network elements and their regulatory roles change actively over time to control the endogenous cell states e.g. different stages in a cell cycle.
A novel network model PathRNet and a reconstruction approach PATTERN are proposed for reconstructing the context specific time varying regulatory networks by integrating microarray gene expression profiles and existing knowledge of pathways and transcription factors. The nodes of the PathRNet are Transcription Factors (TFs) and pathways, and edges represent the regulation between pathways and TFs. The reconstructed PathRNet for Kaposi's sarcoma-associated herpesvirus infection of human endothelial cells reveals the complicated dynamics of the underlying regulatory mechanisms that govern this intricate process. All the related materials including source code are available at http://compgenomics.utsa.edu/tvnet.html webcite.
The proposed PathRNet provides a system level landscape of the dynamics of gene regulatory circuitry. The inference approach PATTERN enables robust reconstruction of the temporal dynamics of pathway-centric regulatory networks. The proposed approach for the first time provides a dynamic perspective of pathway, TF regulations, and their interaction related to specific endogenous and exogenous conditions.