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Dümcke, Sebastian ; Bräuer, Johannes ; Anchang, Benedict Nchang ; Spang, Rainer ; Beerenwinkel, Niko ; Tresch, Achim

Exact likelihood computation in Boolean networks with probabilistic time delays, and its application in signal network reconstruction.

Dümcke, Sebastian, Bräuer, Johannes, Anchang, Benedict Nchang, Spang, Rainer, Beerenwinkel, Niko and Tresch, Achim (2014) Exact likelihood computation in Boolean networks with probabilistic time delays, and its application in signal network reconstruction. Bioinformatics 30 (3), pp. 414-419.

Date of publication of this fulltext: 05 Aug 2014 08:14
Article
DOI to cite this document: 10.5283/epub.30523


Abstract

Motivation: For biological pathways, it is common to measure a gene expression time series after various knockdowns of genes that are putatively involved in the process of interest. These interventional time-resolved data are most suitable for the elucidation of dynamic causal relationships in signaling networks. Even with this kind of data it is still a major and largely unsolved challenge to ...

Motivation: For biological pathways, it is common to measure a gene expression time series after various knockdowns of genes that are putatively involved in the process of interest. These interventional time-resolved data are most suitable for the elucidation of dynamic causal relationships in signaling networks. Even with this kind of data it is still a major and largely unsolved challenge to infer the topology and interaction logic of the underlying regulatory network. Results: In this work, we present a novel model-based approach involving Boolean networks to reconstruct small to medium-sized regulatory networks. In particular, we solve the problem of exact likelihood computation in Boolean networks with probabilistic exponential time delays. Simulations demonstrate the high accuracy of our approach. We apply our method to data of Ivanova et al. (2006), where RNA interference knockdown experiments were used to build a network of the key regulatory genes governing mouse stem cell maintenance and differentiation. In contrast to previous analyses of that data set, our method can identify feedback loops and provides new insights into the interplay of some master regulators in embryonic stem cell development.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleBioinformatics
Publisher:OXFORD UNIV PRESS
Place of Publication:OXFORD
Volume:30
Number of Issue or Book Chapter:3
Page Range:pp. 414-419
DateFebruary 2014
InstitutionsMedicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Informatics and Data Science > Department Computational Life Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Identification Number
ValueType
24292937PubMed ID
10.1093/bioinformatics/btt696DOI
Classification
NotationType
AlgorithmsMESH
AnimalsMESH
Cell DifferentiationMESH
Embryonic Stem Cells/metabolismMESH
Feedback, PhysiologicalMESH
Gene ExpressionMESH
MiceMESH
ProbabilityMESH
RNA InterferenceMESH
Signal TransductionMESH
KeywordsNESTED EFFECTS MODELS; BAYESIAN NETWORKS; REGULATORY NETWORKS; STEM-CELLS; EXPRESSION;
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-305237
Item ID30523

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