Human-yeast genetic interaction for disease network: systematic discovery of multiple drug targets

Abstract

A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by first searching for candidate human disease genes that confer toxicity in yeast, and second, identifying modulators of toxicity. This study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for example. In the subsequent proof-of-concept study focused on ALS, similar functional relationships between a specific kinase and ALS-associated genes were observed in mammalian cells and zebrafish, supporting findings in human-yeast genetic interaction screens. Results of combined analyses highlighted MAP2K5 kinase as a potential therapeutic target in ALS. [BMB Reports 2017; 50(11): 535-536].

Diagram 1

Disease interactome based on human-yeast genetic interaction screens. Human orthologs of yeast genes of which deletion suppressed toxicity of the 20 OMIM ORFs were identified. A network view of human orthologs was generated using Cytoscape. The node color corresponds to the biological function category to which the gene belongs. The color of an edge indicates type of interaction. Adapted from Jo, et al., Genome Res (2017).