GENE NETWORKS IN HUMAN DISEASES

The regulation and function of disease-associated genes is of crucial importance towards understanding molecular mechanisms underlying the disease. The objective of this project is to develop experimental and computational tools to infer the genes and pathway regulated by disease genes and deregulated due to disease-causing mutations. Specifically, we will continue the development of rapid and scalable algorithms that enable construction of a first-order quantitative model of a gene regulatory network using no prior information on the network structure or function, building on our previous efforts. The algorithm will make use of mRNA measurements following perturbation of the expression of the genes in the network. The recovered model will be used to identify the regulatory role of individual genes in the network. In addition, the model can be applied to the RNA expression measurements obtained from pharmacological perturbations to identify the genes that directly mediate a compound’s bioactivity in the cell. We will apply the algorithm to two disease genes: p63 responsible for five human malformation syndromes, and SUMF1 (and its paralog SUMF2) responsible for Multiple Sulphatase Deficiency syndrome.