Expression2Kinases: mRNA Profiling Linked to Multiple Upstream Regulatory Layers
Expression2Kinases was developed by the Ma'ayan Laboratory to identify upstream pathways likely responsible for observed changes in genome-wide gene expression.
Abstract: 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.
Citation: Chen EY, Xu H, Gordonov S, Lim MP, Perkins MH, Ma'ayan A. Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers. Bioinformatics. 2012 Jan 1;28(1):105-11. PMID: 22080467 | PMCID: PMC3244772
Funding: The project was partially funded by NIH grants (P50GM071558-03, R01DK088541-01A1, RC2LM010994-01, P01DK056492-10, RC4DK090860-01 and KL2RR029885-0109).