Computational inference of replication and transcription activator regulator activity in herpesvirus from gene expression data

A. Recchia*, E. Wit, V. Vinciotti, P. Kellam

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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 modi. cations 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 pro. le 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.

    Original languageEnglish
    Pages (from-to)385-396
    Number of pages12
    JournalIet systems biology
    Volume2
    Issue number6
    DOIs
    Publication statusPublished - Nov-2008
    EventWorkshop on Omics - Assembling Systems Biology - , Switzerland
    Duration: 1-Jan-2007 → …

    Keywords

    • transcription activator regulator activity
    • system biology
    • time-course microarray experiment
    • quantitative Michaelis Menten model
    • nonlinear differential equations
    • lytic replication
    • genomic systems
    • gene-regulatory kinetics
    • gene expression data
    • computational inference
    • Rta transcriptional regulator
    • Markov chain Monte Carlo
    • nonlinear differential equations
    • Kaposi sarcoma-associated herpesvirus network
    • Bayesian inferential framework
    • microorganisms
    • genetics
    • medical computing

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