Title
Network-assisted target identification for haploinsufficiency and homozygous profiling screens.
Abstract
Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene's neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug's mechanism of action.
Year
DOI
Venue
2017
10.1371/journal.pcbi.1005553
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Drug discovery,Gene,Phenotype,Biology,Genetic screen,Haploinsufficiency,Comparative genomics,Interaction network,Hop (networking),Bioinformatics,Genetics
Journal
13
Issue
Citations 
PageRank 
6
2
0.36
References 
Authors
2
2
Name
Order
Citations
PageRank
Sheng Wang1498.26
Peng, Jian243050.07