Paper Info
Title
Inference of protein complex activities from chemical-genetic profile and its applications: predicting drug-target pathways.
Abstract
The chemical-genetic profile can be defined as quantitative values of deletion strains' growth defects under exposure to chemicals. In yeast, the compendium of chemical-genetic profiles of genomewide deletion strains under many different chemicals has been used for identifying direct target proteins and a common mode-of-action of those chemicals. In the previous study, valuable biological information such as protein-protein and genetic interactions has not been fully utilized. In our study, we integrated this compendium and biological interactions into the comprehensive collection of,490 protein complexes of yeast for model-based prediction of a drug's target proteins and similar drugs. We assumed that those protein complexes (PCs) were functional units for yeast cell growth and regarded them as hidden factors and developed the PC-based Bayesian factor model that relates the chemical-genetic profile at the level of organism phenotypes to the hidden activities of PCs at the molecular level. The inferred PC activities provided the predictive power of a common mode-of-action of drugs as well as grouping of PCs with similar functions. In addition, our PC-based model allowed us to develop a new effective method to predict a drug's target pathway, by which we were able to highlight the target-protein, TOR1, of rapamycin. Our study is the first approach to model phenotypes of systematic deletion strains in terms of protein complexes. We believe that our PC-based approach can provide an appropriate framework for combining and modeling several types of chemical-genetic profiles including interspecies. Such efforts will contribute to predicting more precisely relevant pathways including target proteins that interact directly with bioactive compounds.
Year
DOI
Venue
2008
10.1371/journal.pcbi.1000162
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
biotechnology,factor model,functional unit,phenotype,cell growth,drug targeting,pharmacogenetics,genetics,bayes theorem,protein complex,drug design,common mode
Gene targeting,Phenotype,Biology,Regulation of gene expression,Fungal protein,Yeast,Bioinformatics,Saccharomyces cerevisiae,Genetics,Bayes' theorem,Organism
Journal
Volume
Issue
ISSN
4
8
1553-7358
Citations 
PageRank 
References 
3
0.57
5
Authors
2
Name
Order
Citations
PageRank
Sangjo Han1462.43
Dongsup Kim232023.11