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Moffa, Giusi ; Erdmann, Gerrit ; Voloshanenko, Oksana ; Hundsrucker, Christian ; Sadeh, Mohammad Javad ; Boutros, Michael ; Spang, Rainer

Refining Pathways: A Model Comparison Approach

Moffa, Giusi, Erdmann, Gerrit, Voloshanenko, Oksana, Hundsrucker, Christian, Sadeh, Mohammad Javad, Boutros, Michael und Spang, Rainer (2016) Refining Pathways: A Model Comparison Approach. PLoS One 11 (6), e0155999.

Veröffentlichungsdatum dieses Volltextes: 16 Jun 2016 07:15
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.33870


Zusammenfassung

Cellular signalling pathways consolidate multiple molecular interactions into working models of signal propagation, amplification, and modulation. They are described and visualized as networks. Adjusting network topologies to experimental data is a key goal of systems biology. While network reconstruction algorithms like nested effects models are well established tools of computational biology, ...

Cellular signalling pathways consolidate multiple molecular interactions into working models of signal propagation, amplification, and modulation. They are described and visualized as networks. Adjusting network topologies to experimental data is a key goal of systems biology. While network reconstruction algorithms like nested effects models are well established tools of computational biology, their data requirements can be prohibitive for their practical use. In this paper we suggest focussing on well defined aspects of a pathway and develop the computational tools to do so. We adapt the framework of nested effect models to focus on a specific aspect of activated Wnt signalling in HCT116 colon cancer cells: Does the activation of Wnt target genes depend on the secretion of Wnt ligands or do mutations in the signalling molecule beta-catenin make this activation independent from them? We framed this question into two competing classes of models: Models that depend on Wnt ligands secretion versus those that do not. The model classes translate into restrictions of the pathways in the network topology. Wnt dependent models are more flexible than Wnt independent models. Bayes factors are the standard Bayesian tool to compare different models fairly on the data evidence. In our analysis, the Bayes factors depend on the number of potential Wnt signalling target genes included in the models. Stability analysis with respect to this number showed that the data strongly favours Wnt ligands dependent models for all realistic numbers of target genes.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftPLoS One
Verlag:PLOS
Ort der Veröffentlichung:SAN FRANCISCO
Band:11
Nummer des Zeitschriftenheftes oder des Kapitels:6
Seitenbereich:e0155999
Datum1 Juni 2016
InstitutionenMedizin > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Informatik und Data Science > Fachbereich Bioinformatik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Identifikationsnummer
WertTyp
10.1371/journal.pone.0155999DOI
27248690PubMed-ID
Stichwörter / KeywordsBETA-CATENIN; COLON-CANCER; MUTATIONS; GENE;
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-338701
Dokumenten-ID33870

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