Dataset Information
Inferring gene targets of drugs and chemical compounds from gene expression profiles.
Ontology highlight
ABSTRACT: Motivation
Finding genes which are directly perturbed or targeted by drugs is of great interest and importance in drug discovery. Several network filtering methods have been created to predict the gene targets of drugs from gene expression data based on an ordinary differential equation model of the gene regulatory network (GRN). A critical step in these methods involves inferring the GRN from the expression data, which is a very challenging problem on its own. In addition, existing network filtering methods require computationally intensive parameter tuning or expression data from experiments with known genetic perturbations or both.Results
We developed a method called DeltaNet for the identification of drug targets from gene expression data. Here, the gene target predictions were directly inferred from the data without a separate step of GRN inference. DeltaNet formulation led to solving an underdetermined linear regression problem, for which we employed least angle regression (DeltaNet-LAR) or LASSO regularization (DeltaNet-LASSO). The predictions using DeltaNet for expression data of Escherichia coli, yeast, fruit fly and human were significantly more accurate than those using network filtering methods, namely mode of action by network identification (MNI) and sparse simultaneous equation model (SSEM). Furthermore, DeltaNet using LAR did not require any parameter tuning and could provide computational speed-up over existing methods.Conclusion
DeltaNet is a robust and numerically efficient tool for identifying gene perturbations from gene expression data. Importantly, the method requires little to no expert supervision, while providing accurate gene target predictions.Availability and implementation
DeltaNet is available on http://www.cabsel.ethz.ch/tools/DeltaNetContact
rudi.gunawan@chem.ethz.chSupplementary information
Supplementary data are available at Bioinformatics online.
SUBMITTER: Noh H
PROVIDER: S-EPMC4937192 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Inferring gene targets of drugs and chemical compounds from gene expression profiles.
Bioinformatics (Oxford, England) 20160318 14
<h4>Motivation</h4>Finding genes which are directly perturbed or targeted by drugs is of great interest and importance in drug discovery. Several network filtering methods have been created to predict the gene targets of drugs from gene expression data based on an ordinary differential equation model of the gene regulatory network (GRN). A critical step in these methods involves inferring the GRN from the expression data, which is a very challenging problem on its own. In addition, existing netw ...[more]