title: Correlation analysis of two-dimensional gel electrophoretic protein patterns and biological variables.
abstract: BACKGROUND
  Two-dimensional gel electrophoresis (2DE) is a powerful technique to examine post-translational modifications of complexly modulated proteins. Currently, spot detection is a necessary step to assess relations between spots and biological variables. This often proves time consuming and difficult when working with non-perfect gels. We developed an analysis technique to measure correlation between 2DE images and biological variables on a pixel by pixel basis. After image alignment and normalization, the biological parameters and pixel values are replaced by their specific rank. These rank adjusted images and parameters are then put into a standard linear Pearson correlation and further tested for significance and variance.
  
  
  RESULTS
  We validated this technique on a set of simulated 2DE images, which revealed also correct working under the presence of normalization factors. This was followed by an analysis of p53 2DE immunoblots from cancer cells, known to have unique signaling networks. Since p53 is altered through these signaling networks, we expected to find correlations between the cancer type (acute lymphoblastic leukemia and acute myeloid leukemia) and the p53 profiles. A second correlation analysis revealed a more complex relation between the differentiation stage in acute myeloid leukemia and p53 protein isoforms.
  
  
  CONCLUSIONS
  The presented analysis method measures relations between 2DE images and external variables without requiring spot detection, thereby enabling the exploration of biosignatures of complex signaling networks in biological systems.
authors.affiliation: Bioinformatics Group, Norut IT, Research Park Tromsø, Postboks 6434, N9294 Tromsø, NO, Norway. werner.van.belle@itek.norut.no
authors.forename: Werner
authors.initials: W
authors.lastname: Van Belle
authors.forename: Nina
authors.initials: N
authors.lastname: Anensen
authors.forename: Ingvild
authors.initials: I
authors.lastname: Haaland
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
authors.forename: Kjell-Arild
authors.initials: KA
authors.lastname: Høgda
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D003198:Computer Simulation; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000032:analysis*; D011499:Protein Processing, Post-Translational; D013223:Statistics as Topic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53