DiGtoP - From Disease Genes to Protein Pathways

Remarkable progress in human genetics has identified mutants in numerous genes that are linked with disease, including neurological and psychiatric diseases, cancer, diabetes, and cardiovascular diseases, amongst others. One of the main problems in moving forward from these discoveries is that genetics identifies individual genes but does not place them into pathways. 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. Therefore, we compare human / mouse protein interactions of relevant disease genes.
Proteomic mapping offers a way forward because it identifies physical relationships and indicates pathways, which can be validated by functional analysis. Proteomic mapping is not straightforward because proteomes are dynamic entities, which include complex variations and fluctuations. Clearly they 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 standardized methodology to place disease genes into pathways will be developed, using recent advances in 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.


Additional relevant Internet links:
DiGTOP