Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data

Melas, IN; Mitsos, A; Messinis, DE; Weiss, TS; Rodriguez, J-S; Alexopoulos, LG

dc.contributor.author	Melas, IN	en
dc.contributor.author	Mitsos, A	en
dc.contributor.author	Messinis, DE	en
dc.contributor.author	Weiss, TS	en
dc.contributor.author	Rodriguez, J-S	en
dc.contributor.author	Alexopoulos, LG	en
dc.date.accessioned	2014-03-01T02:08:34Z
dc.date.available	2014-03-01T02:08:34Z
dc.date.issued	2012	en
dc.identifier.issn	1742206X	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/29668
dc.subject.other	cytokine	en
dc.subject.other	ligand	en
dc.subject.other	phosphoprotein	en
dc.subject.other	article	en
dc.subject.other	biology	en
dc.subject.other	cluster analysis	en
dc.subject.other	drug effect	en
dc.subject.other	feedback system	en
dc.subject.other	human	en
dc.subject.other	metabolism	en
dc.subject.other	methodology	en
dc.subject.other	proteomics	en
dc.subject.other	signal transduction	en
dc.subject.other	statistics	en
dc.subject.other	system analysis	en
dc.subject.other	Cluster Analysis	en
dc.subject.other	Computational Biology	en
dc.subject.other	Cytokines	en
dc.subject.other	Feedback, Physiological	en
dc.subject.other	Humans	en
dc.subject.other	Ligands	en
dc.subject.other	Phosphoproteins	en
dc.subject.other	Programming, Linear	en
dc.subject.other	Proteomics	en
dc.subject.other	Signal Transduction	en
dc.subject.other	Statistics as Topic	en
dc.title	Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data	en
heal.type	journalArticle	en
heal.identifier.primary	10.1039/c2mb05482e	en
heal.identifier.secondary	http://dx.doi.org/10.1039/c2mb05482e	en
heal.publicationDate	2012	en
heal.abstract	Construction of large and cell-specific signaling pathways is essential to understand information processing under normal and pathological conditions. On this front, gene-based approaches offer the advantage of large pathway exploration whereas phosphoproteomic approaches offer a more reliable view of pathway activities but are applicable to small pathway sizes. In this paper, we demonstrate an experimentally adaptive approach to construct large signaling pathways from phosphoproteomic data within a 3-day time frame. Our approach - taking advantage of the fast turnaround time of the xMAP technology - is carried out in four steps: (i) screen optimal pathway inducers, (ii) select the responsive ones, (iii) combine them in a combinatorial fashion to construct a phosphoproteomic dataset, and (iv) optimize a reduced generic pathway via an Integer Linear Programming formulation. As a case study, we uncover novel players and their corresponding pathways in primary human hepatocytes by interrogating the signal transduction downstream of 81 receptors of interest and constructing a detailed model for the responsive part of the network comprising 177 species (of which 14 are measured) and 365 interactions. © 2012 The Royal Society of Chemistry.	en
heal.journalName	Molecular BioSystems	en
dc.identifier.doi	10.1039/c2mb05482e	en
dc.identifier.volume	8	en
dc.identifier.issue	5	en
dc.identifier.spage	1571	en
dc.identifier.epage	1584	en