Probability landscapes for integrative genomics

We introduce here a concept for such a framework, based entirely on systematic annotation in terms of probability profiles of genomic sequence using any type of relevant experimental and theoretical information and subsequent cross-correlation analysis in hypothesis-driven model building and testing.Probability landscapes, which include as reference set the probabilistic representation of the genomic sequence, can be used efficiently to discover and analyze correlations amongst initially heterogeneous and un-relatable descriptions and genome-wide measurements. Furthermore, this structure is usable as a support for automatically generating and testing hypotheses for alternative gene regulatory grammars and the evaluation of those through statistical analysis of the high-dimensional correlations between genomic sequence, sequence annotations, and experimental data. Finally, this structure provides a concrete and tangible basis for attempting to formulate a mathematical description of gene regulation in eukaryotes on a genome-wide scale.The approximately 6,000 to 100,000 genes encoded in different eukaryotic genomes display complex patterns of activity according to the physiological state of the cell and the organism [1]. The resulting cell and cell-state specific transcriptome profiles result from a combination of tightly controlled regulatory events in response to intra-, extra-, and inter-cellular signals [2]. These transcription programs are blurred by different stochastic influences, however, they define the cellular state and activity [3-5]. Almost all known disorders including cancer, genetic syndromes, and pathogen induced diseases are characterized by altered transcriptome profiles [2,6]. Often the molecular basis for pathology is found in affected gene regulatory signaling [6]. Understanding gene regulation therefore required not only for comprehending an organism's physiology but also for developing novel strategies for interference with physiopathology [1,2