Using activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity.

TitleUsing activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity.
Publication TypeJournal Article
Year of Publication2015
AuthorsAmadoz, A, Sebastián-Leon, P, Vidal, E, Salavert, F, Dopazo, J
JournalSci Rep
Volume5
Pagination18494
Date Published2015 Dec 18
ISSN2045-2322
KeywordsAlgorithms; Antineoplastic Agents; biomarkers; Cell Line, Tumor; Cell Survival; gene expression; Humans; Lethal Dose 50; Neoplasms; Phosphorylation; Proteins; Signal Transduction
Abstract

Many complex traits, as drug response, are associated with changes in biological pathways rather than being caused by single gene alterations. Here, a predictive framework is presented in which gene expression data are recoded into activity statuses of signal transduction circuits (sub-pathways within signaling pathways that connect receptor proteins to final effector proteins that trigger cell actions). Such activity values are used as features by a prediction algorithm which can efficiently predict a continuous variable such as the IC50 value. The main advantage of this prediction method is that the features selected by the predictor, the signaling circuits, are themselves rich-informative, mechanism-based biomarkers which provide insight into or drug molecular mechanisms of action (MoA).

DOI10.1038/srep18494
Alternate JournalSci Rep
PubMed ID26678097
PubMed Central IDPMC4683444