Table of Contents
ISRN Computational Biology
Volume 2013, Article ID 719138, 11 pages
http://dx.doi.org/10.1155/2013/719138
Research Article

Effective Single-Step Posttranscriptional Dynamics Allowing for a Direct Maximum Likelihood Estimation of Transcriptional Activity and the Quantification of Sources of Gene Expression Variability with an Illustration for the Hypoxia and TNFα Regulated Inflammatory Pathway

1Center for the Ecological Study of Perception and Action, Department of Psychology, University of Connecticut, 406 Babbidge Road, Storrs, CT 06269, USA
2Systems Biology Ireland (SBI), University College Dublin, Belfield, Dublin 4, Ireland

Received 31 May 2013; Accepted 31 July 2013

Academic Editors: S. Kalyana-Sundaram and B. Oliva

Copyright © 2013 T. D. Frank et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Data analysis methods for estimating promoter activity from gene reporter data frequently involve the reconstruction of the dynamics of unobserved species and numerical search algorithms for determining optimal model parameters. In contrast, we argue that posttranscriptional dynamics effectively behave like a singlestep stochastic process when gene expression variability is relatively low and, half-lives of the unobserved species are relatively small compared to characteristic observation time scales. In this case, by means of maximum likelihood estimators, for which analytical expressions exist, transcriptional activity of gene promoters can be estimated directly from observed gene reporter data without the need for numerical search algorithms and the reconstruction of unobserved variables. In addition, the model-based data analysis approach yields a single variable that measures the effective strength of the sources that give rise to gene expression variability. The approach is applied to conduct a model-based analysis of the inflammatory pathway under hypoxia condition and stimulation with tumor necrosis factor alpha in HEK293 cells.