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Abstract Sensitivity analysis is a popular feature selection approach employed to identify the important features in a dataset. In sensitivity analysis, each input feature is perturbed one-at-a-time and the response of the machine learning model is examined to determine the feature's rank. Note that the existing perturbation techniques may lead to inaccurate feature ranking due to their sensitivity to perturbation parameters. This study proposes a novel approach that involves the perturbation of input features using a complex-step. The implementation of complex-step perturbation in the framework of deep neural networks as a feature selection method is provided in this paper, and its efficacy in determining important features for real-world datasets is demonstrated. Furthermore, the filter-based feature selection methods are employed, and the results obtained from the proposed method are compared. While the results obtained for the classification task indicated that the proposed method outperformed other feature ranking methods, in the case of the regression task, it was found to perform more or less similar to that of other feature ranking methods.
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Network-based drug sensitivity prediction
Abstract Background Drug sensitivity prediction and drug responsive biomarker selection on high-throughput genomic data is a critical step in drug discovery. Many computational methods have been developed to serve this purpose including several deep neural network models. However, the modular relations among genomic features have been largely ignored in these methods. To overcome this limitation, the role of the gene co-expression network on drug sensitivity prediction is investigated in this study. Methods In this paper, we first introduce a network-based method to identify representative features for drug response prediction by using the gene co-expression network. Then, two graph-based neural network models are proposed and both models integrate gene network information directly into neural network for outcome prediction. Next, we present a large-scale comparative study among the proposed network-based methods, canonical prediction algorithms (i.e., Elastic Net, Random Forest, Partial Least Squares Regression, and Support Vector Regression), and deep neural network models for drug sensitivity prediction. All the source code and processed datasets in this study are available at https://github.com/compbiolabucf/drug-sensitivity-prediction . Results In the comparison of different feature selection methods and prediction methods on a non-small cell lung cancer (NSCLC) cell line RNA-seq gene expression dataset with 50 different drug treatments, we found that (1) the network-based feature selection method improves the prediction performance compared to Pearson correlation coefficients; (2) Random Forest outperforms all the other canonical prediction algorithms and deep neural network models; (3) the proposed graph-based neural network models show better prediction performance compared to deep neural network model; (4) the prediction performance is drug dependent and it may relate to the drug’s mechanism of action. Conclusions Network-based feature selection method and prediction models improve the performance of the drug response prediction. The relations between the genomic features are more robust and stable compared to the correlation between each individual genomic feature and the drug response in high dimension and low sample size genomic datasets.
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- Award ID(s):
- 1755761
- PAR ID:
- 10282797
- Date Published:
- Journal Name:
- BMC Medical Genomics
- Volume:
- 13
- Issue:
- S11
- ISSN:
- 1755-8794
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1186/s12920-020-00829-3
