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Sci Rep. 2015 Dec 18;5:18494. doi: 10.1038/srep18494.

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

Author information

1
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
2
Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
3
Functional Genomics Node, (INB) at CIPF, Valencia, Spain.

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).

PMID:
26678097
PMCID:
PMC4683444
DOI:
10.1038/srep18494
[Indexed for MEDLINE]
Free PMC Article

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