title: Quantitative proteomics signature profiling based on network contextualization.
abstract: BACKGROUND
  We present a network-based method, namely quantitative proteomic signature profiling (qPSP) that improves the biological content of proteomic data by converting protein expressions into hit-rates in protein complexes.
  
  
  RESULTS
  We demonstrate, using two clinical proteomics datasets, that qPSP produces robust discrimination between phenotype classes (e.g. normal vs. disease) and uncovers phenotype-relevant protein complexes. Regardless of acquisition paradigm, comparisons of qPSP against conventional methods (e.g. t-test or hypergeometric test) demonstrate that it produces more stable and consistent predictions, even at small sample size. We show that qPSP is theoretically robust to noise, and that this robustness to noise is also observable in practice. Comparative analysis of hit-rates and protein expressions in significant complexes reveals that hit-rates are a useful means of summarizing differential behavior in a complex-specific manner.
  
  
  CONCLUSIONS
  Given qPSP's ability to discriminate phenotype classes even at small sample sizes, high robustness to noise, and better summary statistics, it can be deployed towards analysis of highly heterogeneous clinical proteomics data.
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Tianjin City, 300072, China. wilson.goh@tju.edu.cn.|Center for Interdisciplinary Cardiovascular Sciences, Harvard Medical School, Boston, USA. wilson.goh@tju.edu.cn.|Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. wilson.goh@tju.edu.cn.|School of Computing, National University of Singapore, Singapore, Singapore. wilson.goh@tju.edu.cn.
authors.forename: Wilson Wen
authors.initials: WW
authors.lastname: Bin Goh
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. guo@imsb.biol.ethz.ch.
authors.forename: Tiannan
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. aebersold@imsb.biol.ethz.ch.|Faculty of Science, University of Zurich, Zurich, Switzerland. aebersold@imsb.biol.ethz.ch.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: School of Computing, National University of Singapore, Singapore, Singapore. wongls@comp.nus.edu.sg.
authors.forename: Limsoon
authors.initials: L
authors.lastname: Wong
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*