Expression2Kinases: MRNA Profiling Linked to Multiple Upstream Regulatory Layers

Overview

Journal Bioinformatics

Publisher Oxford University Press

Specialty Biology

Date 2011 Nov 15

PMID 22080467

Citations 99

Authors

Edward Y Chen

Huilei Xu

Simon Gordonov

Maribel P Lim

Matthew H Perkins

Avi Maayan

Affiliations

Soon will be listed here.

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.

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