Disease co-morbidity and the human Wnt signaling pathway: a network-wise study.

The human Wnt signaling pathway contains 57 genes communicating among themselves by 70 experimentally established associations, as given in the KEGG/PATHWAY database. It is responsible for a variety of crucial biological functions such as regulation of cell fate determination, proliferation, differentiation, migration, and apoptosis. Abnormal behavior of its members causes numerous types of human cancers, dramatic changes in bone mass density that lead to diseases such as osteoporosis-pseudo-glioma syndrome, Van-Buchem disease, skeletal malformation, autosomal dominant sclerosteosis, and osteoporosis type I syndromes. So far, single genes have been investigated for their disease-causing properties, and single diseases have been traced backwards to discover foul-play of the system pathways. Differential expression of the whole genome has been mapped by microarray. But how all the genes involved in a pathway affect each other in single/multiple disease state(s) and whether the presence of one disease state makes a person prone to another kind of disease(s) (i.e., comorbidity among diseases associated with a certain important biological pathway) is still unknown. We have developed a human Wnt signaling pathway diseasome and analyzed it for finding answers to such questions. Data used in constructing the diseasome can be downloaded from the publicly accessible webserver http://www.isical.ac.in/-rajat/diseasome/index.php.