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Pirkl, Martin ; Hand, E. ; Kube, D. ; Spang, Rainer

Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models

Pirkl, Martin, Hand, E., Kube, D. and Spang, Rainer (2015) Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models. Bioinformatics.

Date of publication of this fulltext: 27 Nov 2015 14:21
Article
DOI to cite this document: 10.5283/epub.32910


Abstract

Motivation: Understanding the structure and interplay of cellular signalling pathways is one of the great challenges in molecular biology. Boolean Networks can infer signalling networks from observations of protein activation. In situations where it is difficult to assess protein activation directly, Nested Effect Models are an alternative. They derive the network structure indirectly from ...

Motivation: Understanding the structure and interplay of cellular signalling pathways is one of the great challenges in molecular biology. Boolean Networks can infer signalling networks from observations of protein activation. In situations where it is difficult to assess protein activation directly, Nested Effect Models are an alternative. They derive the network structure indirectly from downstream effects of pathway perturbations. To date, Nested Effect Models cannot resolve signalling details like the formation of signalling complexes or the activation of proteins by multiple alternative input signals. Here we introduce Boolean Nested Effect Models (B-NEM). B-NEMs combine the use of downstream effects with the higher resolution of signalling pathway structures in Boolean Networks. Results: We show that B-NEMs accurately reconstruct signal flows in simulated data. Using B-NEM we then resolve BCR signalling via PI3K and TAK1 kinases in BL2 lymphoma cell lines.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleBioinformatics
Publisher:Oxford Univ. Press
Place of Publication:OXFORD
DateNovember 2015
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
10.1093/bioinformatics/btv680DOI
26581413PubMed ID
KeywordsNF-KAPPA-B; FUNCTIONAL-ANALYSIS; NETWORKS; RECONSTRUCTION; ACTIVATION; EXPRESSION; ALGORITHM; SURVIVAL; SUBSET; CELLS;
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
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-329102
Item ID32910

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