Correlation analysis of two-dimensional gel electrophoretic protein patterns and biological variables

Werner Van Belle¹^* - werner@yellowcouch.org, werner.van.belle@gmail.com
Nina Ånensen²
Ingvild Haaland²
Oystein Bruserud^2,3
Kjell-Arild Høgda⁴ - kah@itek.norut.no
Bjørn Tore Gjertsen^2,3 - bjorn.gjertsen@med.uib.no

1- Bioinformatics Group; Norut IT; Research Park; 9294 Tromsø; Norway
2- Institute of Medicine; Hematology Section; University of Bergen; Haukeland University Hospital; Bergen; Norway
3- Department of Internal Medicine; Hematology Section; Haukeland University Hospital; Bergen; Norway
4- Earth Observation Group; Norut IT; Research Park; 9294 Tromsø; Norway
* Corresponding author

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. Conclusion) 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.

Keywords: 2D electrophoretic gels, correlation, 2D gel analysis, P53 FAB classifications, AML, ALL
Reference: Werner Van Belle, Nina Ånensen, Ingvild Haaland, Oystein Bruserud, Kjell-Arild Høgda, Bjørn Tore Gjertsen; Correlation analysis of two-dimensional gel electrophoretic protein patterns and biological variables; BMC Bioinformatics; volume 7; nr 198; April 2006
Files: bmc06.pdf
See also: Outline of the method

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