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) 28 (1): 105-111 [PubMed]

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The X2K Workflow

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 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. The idea is to first infer the most likely transcription factors that regulate the differences in gene expression, then use protein-protein interactions to connect the identified transcription factors using additional proteins for building transcriptional regulatory subnetworks centered on these factors, and finally use kinase-substrate protein phosphorylation reactions, to identify and rank candidate protein-kinases that most likely regulate the formation of the identified transcriptional complexes. The X2K approach can advance our understanding of cell signaling and unravel drugs mechanisms of action.