Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/47805

TitleData-driven reverse engineering of signaling pathways using ensembles of dynamic models
Author(s)Henriques, David
Villaverde, Alejandro F.
Rocha, Miguel
Saez-Rodriguez, Julio
Banga, Julio R.
Issue date6-Feb-2017
PublisherPublic Library of Science (PLOS)
JournalPLoS Computational Biology
CitationHenriques, David; Villaverde, Alejandro F.; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R., Data-driven reverse engineering of signaling pathways using ensembles of dynamic models. PLoS Computational Biology, 13(2), 1-25, 2017
Abstract(s)Signaling pathways play a key role in complex diseases such as cancer, for which the development of novel therapies is a difficult, expensive and laborious task. Computational models that can predict the effect of a new combination of drugs without having to test it experimentally can help in accelerating this process. In particular, network-based dynamic models of these pathways hold promise to both understand and predict the effect of therapeutics. However, their use is currently hampered by limitations in our knowledge of the underlying biochemistry, as well as in the experimental and computational technologies used for calibrating the models. Thus, the results from such models need to be carefully interpreted and used in order to avoid biased predictions. Here we present a procedure that deals with this uncertainty by using experimental data to build an ensemble of dynamic models. The method incorporates steps to reduce overfitting and maximize predictive capability. We find that by combining the outputs of individual models in an ensemble it is possible to obtain a more robust prediction. We report results obtained with this method, which we call SELDOM (enSEmbLe of Dynamic lOgic-based Models), showing that it improves the predictions previously reported for several challenging problems.
TypeArticle
URIhttp://hdl.handle.net/1822/47805
DOI10.1371/journal.pcbi.1005379
ISSN1553-734X
e-ISSN1553-7358
Publisher versionhttp://journals.plos.org/ploscompbiol/
Peer-Reviewedyes
AccessOpen access
Appears in Collections:CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series

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