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. © 2008 The Institution of Engineering and Technology.

Computational inference of replication and transcription activator regulator activity in herpesvirus from gene expression data / Recchia, A.; Wit, E.; Vinciotti, V.; Kellam, P.. - In: IET SYSTEMS BIOLOGY. - ISSN 1751-8849. - 2:6(2008), pp. 385-396. [10.1049/iet-syb:20070053]

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

Vinciotti V.;
2008-01-01

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. © 2008 The Institution of Engineering and Technology.
2008
6
Recchia, A.; Wit, E.; Vinciotti, V.; Kellam, P.
Computational inference of replication and transcription activator regulator activity in herpesvirus from gene expression data / Recchia, A.; Wit, E.; Vinciotti, V.; Kellam, P.. - In: IET SYSTEMS BIOLOGY. - ISSN 1751-8849. - 2:6(2008), pp. 385-396. [10.1049/iet-syb:20070053]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/275990
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