BMC Systems Biology: BRCA-Monet: a breast cancer specific drug treatment mode-of-action network for treatment effective prediction using large scale microarray database
Chifeng Ma, Hung-I Harry Chen, Mario Flores, Yufei Huang & Yidong Chen
Abstract
Background
Connectivity map (cMap) is a recently developed dataset and algorithm for uncovering and understanding the treatment effect of small molecules on different cancer cell lines. It is widely used but there are still remaining challenges for accurate predictions.
Method
Here, we propose BRCA-MoNet, a network of drug mode of action (MoA) specific to breast cancer, which is constructed based on the cMap dataset. A drug signature selection algorithm fitting the characteristic of cMap data, a quality control scheme as well as a novel query algorithm based on BRCA-MoNet are developed for more effective prediction of drug effects.
Result
BRCA-MoNet was applied to three independent data sets obtained from the GEO database: Estrodial treated MCF7 cell line, BMS-754807 treated MCF7 cell line and a breast cancer patient microarray dataset. In the first case, BRCA-MoNet could identify drug MoAs likely to share the same and reverse treatment effect. In the second case, the result demonstrated the potential of BRCA-MoNet to reposition drugs and predict treatment effects for drugs, not in cMap data. In the third case, a possible procedure for personalized drug selection is showcased.
Conclusions
The results clearly demonstrated that the proposed BRCA-MoNet approach can provide increased prediction power to cMap and thus will be useful for the identification of new therapeutic candidates.
Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.
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