Introduction
Human genetics have identified mutants in numerous genes that are linked with disease, including neurological and psychiatric diseases, cancer, diabetes, and cardiovascular diseases, amongst others. However, it has been difficult, especially for novel genes, to determine how mutations cause disease. In addition, disease models often do not recapitulate human disease phenotypes probably due to differences in protein interaction. Moving forward from these discoveries human disease genes need to be placed into regulatory and structural networks.
We believe that proteomic mapping is essential in order to face this challenge because it identifies physical relationships and indicates pathways between individual genes, which can be validated by functional analysis. Proteomes are dynamic entities that clearly cannot be completely defined in the same way that a genome sequence can. However, proteomes have stable cores that can be mapped. This map can then serve as the scaffold for understanding transient and regulated interactions.
In the framework of DiGtoP, we will develop standardized methodology to place disease genes into pathways, building upon recent advances into genomics and proteomics. This approach, complemented by reciprocal validation and functional studies, will establish a mammalian proteomic database relevant to disease pathways and therapy and a pipeline for study of novel disease genes as they are discovered.