Approaching the Sequential and Three-Dimensional Organization of Genomes

Genomes are one of the major foundations of life due to their role in information storage, process regulation and evolution. To achieve a deeper unterstanding of the human genome the three-dimensional organization of the human cell nucleus, the structural-, scaling- and dynamic properties of interphase chromosomes and cell nuclei were simulated and combined with the analysis of their sequential organization and (in vivo) experiments: The Multi-Loop-Subcompartment model is currently in best agreement with experiment concerning formation and overlap of chromosomes, -territories -arms and subcompartments. Even small model changes lead to pathological recognisable morphologic differences. Review and comparison of experimental to simulated spatial distances between genomic markers even lead to specifics as a chromatin loop size of 63 to 126 kbp. Correlation analyses on the DNA sequence level of completely sequenced Archaea, Bacteria and Eukarya revealed fine- structured positive multi-scaling long-range correlations being again in agreement. Simulations and experiments agree also in the diffusion behaviour of biologically relevant tracers being only moderately obstructed. Thus, the local, global and dynamic genome characteristics are tightly inter-connected and integrated holisticly to fulfill their function. On this bases we also developed the first system-biology oriented genome browser - the GLOBE 3D Genome Viewer - necessary to access, present, annotate, and to simulate this holistic complexity in a unique gateway towards a real understanding, educative presentation and curative manipulation planning of genomes. Additionally, we currently set-up the Erasmus Computing Grid for the enormous computational needs of live- science research and diagnostics. With 3 Tera flops and reaching 20 Tera flops in the first set-up phase the ECG is one of the worlds largest desktop computing grids.