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Bioinformatics Advance Access published online on August 21, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn446
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Analyzing Gene Perturbation Screens With Nested Effects Models in R and Bioconductor

Holger Fröhlich a, Tim Beißbarth a, Achim Tresch b, Dennis Kostka c, Juby Jacob d, Rainer Spang d,* and F. Markowetz e

a German Cancer Research Center (DKFZ), INF 580, 69120 Heidelberg, Germany; b Gene Center, Ludwigs-Maximilian-Universität München, Germany; c Genome Center and Dept. of Statistics, University of California Davis, Davis CA 95616, USA; d Computational Diagnostics Group, Institute of Functional Genomics, University of Regensburg, 93053 Regensburg, Germany; e Lewis-Sigler Institute for Integrative Genomics and Dept. of Computer Science, Princeton University, Princeton NJ 08544, USA

*To whom correspondence should be addressed. Rainer Spang, E-mail: rainer.spang{at}klinik.uni-regensburg.de


  Abstract

Summary: Nested Effects Models (NEMs) are a class of probabilistic models introduced to analyze the effects of gene perturbation screens visible in high-dimensional phenotypes like microarrays or cell morphology. NEMs reverse engineer upstream/downstream relations of cellular signaling cascades. NEMs take as input a set of candidate pathway genes and phenotypic profiles of perturbing these genes. NEMs return a pathway structure explaining the observed perturbation effects. Here we describe the package nem, an open-source software to efficiently infer NEMs from data. Our software implements several search algorithms for model fitting and is applicable to a wide range of different data types and representations. The methods we present summarize the current state-of-the-art in Nested Effects Models.

Availability: Our software is written in the R language and freely available via the Bioconductor project at http://www.bioconductor.org.

Contact: rainer.spang{at}klinik.uni-regensburg.de

Associate Editor: Dr. Jonathan Wren

Received on June 25, 2008; revised on August 12, 2008; accepted on August 17, 2008

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 Proc. Natl. Acad. Sci. USAHome page
B. Anchang, M. J. Sadeh, J. Jacob, A. Tresch, M. O. Vlad, P. J. Oefner, and R. Spang
Special Feature: Complex Systems: From Chemistry to Systems Biology Special Feature: Modeling the temporal interplay of molecular signaling and gene expression by using dynamic nested effects models
PNAS, April 21, 2009; 106(16): 6447 - 6452.
[Abstract] [Full Text] [PDF]


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