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Bioinformatics. 2012 Jan 1;28(1):105-11. doi: 10.1093/bioinformatics/btr625. Epub 2011 Nov 10.

Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers.

Author information

1
Department of Pharmacology and Systems Therapeutics, Systems Biology Center New York, New York, NY, USA.

Abstract

MOTIVATION:

Genome-wide mRNA profiling provides a snapshot of the global state of cells under different conditions. However, mRNA levels do not provide direct understanding of upstream regulatory mechanisms. Here, we present a new approach called Expression2Kinases (X2K) to identify upstream regulators likely responsible for observed patterns in genome-wide gene expression. By integrating chromatin immuno-precipitation (ChIP)-seq/chip and position weight matrices (PWMs) data, protein-protein interactions and kinase-substrate phosphorylation reactions, we can better identify regulatory mechanisms upstream of genome-wide differences in gene expression. We validated X2K by applying it to recover drug targets of food and drug administration (FDA)-approved drugs from drug perturbations followed by mRNA expression profiling; to map the regulatory landscape of 44 stem cells and their differentiating progeny; to profile upstream regulatory mechanisms of 327 breast cancer tumors; and to detect pathways from profiled hepatic stellate cells and hippocampal neurons. The X2K approach can advance our understanding of cell signaling and unravel drugs mechanisms of action.

AVAILABILITY:

The software and source code are freely available at: http://www.maayanlab.net/X2K.

CONTACT:

avi.maayan@mssm.edu

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

PMID:
22080467
PMCID:
PMC3244772
DOI:
10.1093/bioinformatics/btr625
[Indexed for MEDLINE]
Free PMC Article

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