PASCAL - Pattern Analysis, Statistical Modelling and Computational Learning

A probabilistic dynamical model for quantitative inference of the regulatory mechanism of transcription
Guido Sanguinetti, Magnus Rattray and Neil Lawrence
Bioinformatics Volume 22, Number 14, pp. 1753-1759, 2006.

Abstract

\section{Motivation}Quantitative estimation of the regulatory relationship between transcription factors and genes is a fundamental stepping stone when trying to develop models of cellular processes. This task, however, is difficult for a number of reasons: transcription factors' expression levels are often low and noisy, and many transcription factors are post-transcriptionally regulated. It is therefore useful to infer the activity of the transcription factors from the expression levels of their target genes. \section{Results}We introduce a novel probabilistic model to infer transcription factor activities from microarray data when the structure of the regulatory network is known. The model is based on regression, retaining the computational efficiency to allow genome-wide investigation, but is rendered more flexible by sampling regression coefficients independently for each gene. This allows us to determine the strength with which a transcription factor regulates each of its target genes, therefore providing a quantitative description of the transcriptional regulatory network. The probabilistic nature of the model also means that we can associate credibility intervals to our estimates of the activities. We demonstrate our model on two yeast data sets. In both cases the network structure was obtained using Chromatine Immunoprecipitation data. We show how predictions from our model are consistent with the underlying biology and offer novel quantitative insights into the regulatory structure of the yeast cell. \section{Availability} MATLAB code is available from \texttt{http://umber.sbs.man.ac.uk/resources/puma}.

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EPrint Type:Article
Project Keyword:Project Keyword UNSPECIFIED
Subjects:Learning/Statistics & Optimisation
ID Code:2240
Deposited By:Guido Sanguinetti
Deposited On:28 October 2006