Tuesday, March 19, 2013

FAQ: What is the human gene connectome?

As a result of high through-put genome sequencing technologies a plethora of data can be generated from patient samples. However, this data can take a lot of time to search through in order to find the relevant disease causing mutation in a monogenic disease hidden within this data. In hopes of making this search more directed, a collaboration of scientist from the US, France and Israel sought to design a computer program that would determine the biological distance between every gene in the human genome. The report on the human gene connectome (HGC) appears in PNAS.

The HGC is based on what has been discovered about the protein-protein interactions and molecular pathways in which gene products exist and applies a numerical value to how closely connected two genes are. As support of principal the group applied this approach to a disease. They studied the pathogenesis of herpes simplex virus 1 (HSV-1) encephalitis (HSE). Inborn errors of Toll-like receptor 3 (TLR-3) have been shown to be important in HSE pathogenesis, so they developed a TLR-3 specific connectome. The results confirmed what many had previously shown regarding other genes in the molecular pathway which when mutated are also associated with the disease state. In particular, when genetic data from two patients was compared they were both confirmed to have a mutation in TANK-binding kinase which is a biologically close gene and has previously been associated with HSE.

The authors believe that using the HGC will significantly increase the discovery of disease-causing genes by solving the needle in a haystack problems associated with extensive genetic data sets. The HGC program is freely available to noncommercial users:  http://lab.rockefeller.edu/casanova/HGC

Article: The human gene connectome as a map of short cuts for morbid allele discovery