Nature Biotechnology
- 24, 1270 - 1278 (2006)
Published online: 1 October 2006; | doi:10.1038/nbt1250
Analyzing proteome topology and function by automated multidimensional fluorescence microscopyWalter Schubert1, 5, Bernd Bonnekoh2, Ansgar J Pommer5, Lars Philipsen5, Raik Böckelmann2, Yanina Malykh5, Harald Gollnick2, Manuela Friedenberger1, 6, Marcus Bode1, 5, 6 & Andreas W M Dress3, 4, 61
Molecular Pattern Recognition Research (MPRR) Group, Institute of Medical Neurobiology, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany. 2
Clinic for Dermatology and Venereology, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany. 3
CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences (SIBS), CN-200031 Shanghai, China. 4
MPI for Mathematics in the Sciences, D-04103 Leipzig, Germany. 5
ZENIT Technology Park, D-39120 Magdeburg, Germany. 6
These authors contributed equally to this work.
Correspondence should be addressed to Walter Schubert walter.schubert@medizin.uni-magdeburg.de Temporal and spatial regulation of proteins contributes to function. We describe a multidimensional microscopic robot technology for high-throughput protein colocalization studies that runs cycles of fluorescence tagging, imaging and bleaching in situ. This technology combines three advances: a fluorescence technique capable of mapping hundreds of different proteins in one tissue section or cell sample; a method selecting the most prominent combinatorial molecular patterns by representing the data as binary vectors; and a system for imaging the distribution of these protein clusters in a so-called toponome map. By analyzing many cell and tissue types, we show that this approach reveals rules of hierarchical protein network organization, in which the frequency distribution of different protein clusters obeys Zipf's law, and state-specific lead proteins appear to control protein network topology and function. The technology may facilitate the development of diagnostics and targeted therapies.
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