X2K (Expression2Kinases) is a method 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, X2K can better identify regulatory mechanisms upstream of genome-wide differences in gene expression. X2K first infers 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.
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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