RT Journal
A1 Jo, Myungjin
A1 Chung, Ah Young
A1 Yachie, Nozomu
A1 Seo, Minchul
A1 Jeon, Hyejin
A1 Nam, Youngpyo
A1 Seo, Yeojin
A1 Kim, Eunmi
A1 Zhong, Quan
A1 Vidal, Marc
A1 Park, Hae Chul
A1 Roth, Frederick P.
A1 Suk, Kyoungho
T1 Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target
JF Genome Research 
JO Genome Research 
YR 2017 
FD September 01 
VO 27 
IS 9 
SP 1487 
OP 1500 
DO 10.1101/gr.211649.116 
UL http://genome.cshlp.org/content/27/9/1487.abstract 
AB To understand disease mechanisms, a large-scale analysis of human–yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human–yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin (OPTN) and angiogenin (ANG), showed that the human orthologs of the yeast toxicity modifiers of these ALS genes are enriched for several biological processes, such as cell death, lipid metabolism, and molecular transport. When yeast genetic interaction partners held in common between human OPTN and ANG were validated in mammalian cells and zebrafish, MAP2K5 kinase emerged as a potential drug target for ALS therapy. The toxicity modifiers identified in this study may deepen our understanding of the pathogenic mechanisms of ALS and other devastating diseases.