JEDI approach to the disease gene discovery

One of the most important challenges of contemporary biology and medicine is establishing the relationship between disease phenotypes and disruptions of the underlying cellular functions. In the past decades, significant efforts have been devoted to a gene-based approach, and identifying the specific genetic defects that, together with single nucleotide polymorphisms and copy number variations, predispose an organism to disease. Such an approach, although successful, is still not sufficient for understanding of pathophysiology of genetic disorders. Indeed, most cellular components perform their functions through complicated networks of regulatory, metabolic, and protein interactions. Therefore, the impact of different genetic and epigenetic variations may propagate in the intracellular network, affecting the function of genes and gene products that otherwise carry no defects. Such intricate interdependencies between cellular components create a possibility of functional and causal relationships between apparently distinct disease phenotypes. [Lee and Barabasi, 2005].

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