Abstract
Purpose :
Retinitis Pigmentosa (RP) is a rare monogenic retinal disease that causes the atrophy of photoreceptor, cone and rod cells. Based on the defect of even a single causal gene converging at the same disease, we hypothesized that all of the genes that cause RP must be connected to each other through protein-protein interactions (PPIs) in this computational correlation study.
Methods :
A final list of 161 genes that are known to cause RP was compiled using RetNet (https://sph.uth.edu/RetNet/) on Feb. 15, 2019. Of 161 genes, 159 were recognized and mapped by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), which uses PPIs as the measure of association. On the basis of the hypothesized interconnectedness among RP genes, we defined novel genes as the genes that may cause RP by interacting with the genes already attributed to the disease. The novel genes, which connect the ten previously disconnected genes, were then identified based on the PPI confidence levels to complete the network of RP genes. Further reorganization based on subcellular localization and previous literature of the 169 genes was conducted for analysis.
Results :
Ten novel genes were discovered through PPIs at a minimum of 40% confidence for the initial 161 genes (Figure 2a). The categorization of cells based on subcellular localization showed that the genes with protein products localized in the rod outer segment (ROS) have the greatest number of PPIs. With the inclusion of these novel genes, all known causal genes of RP were connected to each other as hypothesized.
Conclusions :
The successful establishment of PPIs among all documented genes and the discovery of novel genes for Retinitis Pigmentosa strongly support the global interconnectedness of the genes that cause the disease on the molecular level as hypothesized. Furthermore, the additional findings such as the greatest number of PPIs with respect to ROS and previous literature on the association of novel genes to RP support the hypothesis that all genes that cause Retinitis Pigmentosa must be interconnected.
This is a 2021 ARVO Annual Meeting abstract.