title: PhosphoChain: a novel algorithm to predict kinase and phosphatase networks from high-throughput expression data.
abstract: BACKGROUND
  Protein phosphorylation is critical for regulating cellular activities by controlling protein activities, localization and turnover, and by transmitting information within cells through signaling networks. However, predictions of protein phosphorylation and signaling networks remain a significant challenge, lagging behind predictions of transcriptional regulatory networks into which they often feed.
  
  
  RESULTS
  We developed PhosphoChain to predict kinases, phosphatases and chains of phosphorylation events in signaling networks by combining mRNA expression levels of regulators and targets with a motif detection algorithm and optional prior information. PhosphoChain correctly reconstructed ∼78% of the yeast mitogen-activated protein kinase pathway from publicly available data. When tested on yeast phosphoproteomic data from large-scale mass spectrometry experiments, PhosphoChain correctly identified ∼27% more phosphorylation sites than existing motif detection tools (NetPhosYeast and GPS2.0), and predictions of kinase-phosphatase interactions overlapped with ∼59% of known interactions present in yeast databases. PhosphoChain provides a valuable framework for predicting condition-specific phosphorylation events from high-throughput data.
  
  
  BACKGROUND
  PhosphoChain is implemented in Java and available at http://virgo.csie.ncku.edu.tw/PhosphoChain/ or http://aitchisonlab.com/PhosphoChain
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109-5234, USA, Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan and Seattle Biomedical Research Institute, Seattle, WA 98109-5219, USA.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Danziger
authors.forename: Jung-Hsien
authors.initials: JH
authors.lastname: Chiang
authors.forename: John D
authors.initials: JD
authors.lastname: Aitchison
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D015971:Gene Expression Regulation, Enzymologic; D016678:Genome; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases