1. Home page
  2. Search

Combined logical and data-driven models for linking signalling pathways to cellular response

This item is provided by the institution :
National Technical University of Athens   

Repository :
Digital Library of National Technical University of Athens | Dspace@NTUA   

see the original item page
in the repository's web site and access all digital files if the item*



Combined logical and data-driven models for linking signalling pathways to cellular response (EN)
Melas, IN (EN)
Weiss, TS (EN)
Alexopoulos, LG (EN)
Mitsos, A (EN)
Messinis, DE (EN)
journalArticle (EN)
2014-03-01T01:35:25Z
2011 (EN)
Background: Signalling pathways are the cornerstone on understanding cell function and predicting cell behavior. Recently, logical models of canonical pathways have been optimised with high-throughput phosphoproteomic data to construct cell-type specific pathways. However, less is known on how signalling pathways can be linked to a cellular response such as cell growth, death, cytokine secretion, or transcriptional activity.Results: In this work, we measure the signalling activity (phosphorylation levels) and phenotypic behavior (cytokine secretion) of normal and cancer hepatocytes treated with a combination of cytokines and inhibitors. Using the two datasets, we construct ""extended"" pathways that integrate intracellular activity with cellular responses using a hybrid logical/data-driven computational approach. Boolean logic is used whenever a priori knowledge is accessible (i.e., construction of canonical pathways), whereas a data-driven approach is used for linking cellular behavior to signalling activity via non-canonical edges. The extended pathway is subsequently optimised to fit signalling and behavioural data using an Integer Linear Programming formulation. As a result, we are able to construct maps of primary and transformed hepatocytes downstream of 7 receptors that are capable of explaining the secretion of 22 cytokines.Conclusions: We developed a method for constructing extended pathways that start at the receptor level and via a complex intracellular signalling pathway identify those mechanisms that drive cellular behaviour. Our results constitute a proof-of-principle for construction of ""extended pathways"" that are capable of linking pathway activity to diverse responses such as growth, death, differentiation, gene expression, or cytokine secretion. © 2011 Melas et al; licensee BioMed Central Ltd. (EN)
Mathematical & Computational Biology (EN)
Signalling Pathway (EN)
High Throughput (EN)
HEPATOCYTES (EN)
ACTIVATION (EN)
TRANSDUCTION (EN)
Integer Linear Program (EN)
TUMOR-CELLS (EN)
NETWORKS (EN)
CANCER (EN)
Differential Gene Expression (EN)
Proof of Principle (EN)
GROWTH-FACTOR RECEPTOR (EN)
HEPATOCELLULAR-CARCINOMA (EN)
a priori knowledge (EN)
Hybrid Logic (EN)
INFLAMMATION (EN)
Cell Growth (EN)
TYROSINE KINASE INHIBITOR (EN)
BMC Systems Biology (EN)
English
BIOMED CENTRAL LTD (EN)
National Technical University of Athens
Digital Library of National Technical University of Athens | Dspace@NTUA
Κεντρική Βιβλιοθήκη Ε.Μ.Π.
Ιδρυματικό Αποθετήριο
Δημοσιεύσεις μελών Δ.Ε.Π. σε περιοδικά



*Institutions are responsible for keeping their URLs functional (digital file, item page in repository site)