title: Computational inference of replication and transcription activator regulator activity in herpesvirus from gene expression data.
abstract: One of the main aims of system biology is to understand the structure and dynamics of genomic systems. A computational approach, facilitated by new technologies for high-throughput quantitative experimental data, is put forward to investigate the regulatory system of dynamic interaction among genes in Kaposi's sarcoma-associated herpesvirus network after induction of lytic replication. A reconstruction of transcription factor activity and gene-regulatory kinetics using data from a time-course microarray experiment is proposed. The computational approach uses nonlinear differential equations. In particular, the quantitative Michaelis-Menten model of gene-regulatory kinetics is extended to allow for post-transcriptional modifications and synergic interactions between target genes and the Rta transcription factor. The kinetic method is developed within a Bayesian inferential framework using Markov chain Monte Carlo. The profile of the Rta transcriptional regulator, other post-transcriptional regulatory genes and gene-specific kinetic parameters are inferred from the gene expression data of the target genes. The method described here provides an example of a principled approach to handle a wide range of transcriptional network architectures and regulatory activation mechanisms to reconstruct the activity of several transcription factors and activation kinetic parameters in a single regulatory network.
authors.affiliation: University of Groningen (RUG), Institute of Mathematics and Computing Science, Groningen, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Recchia
authors.forename: E
authors.initials: E
authors.lastname: Wit
authors.forename: V
authors.initials: V
authors.lastname: Vinciotti
authors.forename: P
authors.initials: P
authors.lastname: Kellam
mesh_terms: D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D014157:Transcription Factors; D014764:Viral Proteins