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Reconstructing transcription factor activities in hierarchical transcription network motifs

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2873-2879
Number of pages7
JournalBioinformatics
Volume27
Issue number20
DOIs
Publication statusPublished - 2011

Abstract

Motivation: A knowledge of the dynamics of transcription factors is fundamental to understand the transcriptional regulation mechanism. Nowadays, an experimental measure of transcription factor activities in vivo represents a challenge. Several methods have been developed to infer these activities from easily measurable quantities such as mRNA expression of target genes. A limitation of these methods is represented by the fact that they rely on very simple single-layer structures, typically consisting of one or more transcription factors regulating a number of target genes.Results: We present a novel statistical inference methodology to reverse engineer the dynamics of transcription factors in hierarchical network motifs such as feed-forward loops. The approach we present is based on a continuous time representation of the system where the high-level master transcription factor is represented as a two state Markov jump process driving a system of differential equations. We solve the inference problem using an efficient variational approach and demonstrate our method on simulated data and two real datasets. The results on real data show that the predictions of our approach can capture biological behaviours in a more effective way than single-layer models of transcription, and can lead to novel biological insights.Availability: http://homepages.inf.ed.ac.uk/gsanguin/software.htmlContact: g.sanguinetti@ed.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.

ID: 21809118