Protein-protein-interactions (PPIs) are fundamental to all cellular processes. Recently, large human interaction maps have been generated using high throughput technologies such as the yeast two hybrid system (Y2H) or affinity chromatography and mass spectrometry. However, the resulting networks are static, incomplete and not disease specific. To address these limitations, we have developed an integrated functional genomics strategy that combinesY2H interaction and gene expression studies in order to create tissue specific disease networks. A network for Huntington’s disease was generated and subsequently validated in vitro and in vivo (cell and Drosophila models). In this way, the huntingtin interaction partner CRMP1 (collapsin response mediator protein1) was identified as a novel modulator of Huntington’s disease pathogenesis. We propose that tissue specific PPI networks are valuable resources for disease research, providing essential clues to protein function. Also, they do not provide immediate clues about disease processes and modifiers.
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