title: Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  The software and source code are freely available at: http://www.maayanlab.net/X2K.
  
  
  BACKGROUND
  avi.maayan@mssm.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Systems Biology Center New York, New York, NY, USA.
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Chen
authors.forename: Huilei
authors.initials: H
authors.lastname: Xu
authors.forename: Simon
authors.initials: S
authors.lastname: Gordonov
authors.forename: Maribel P
authors.initials: MP
authors.lastname: Lim
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Perkins
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D012984:Software; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
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