Dataset Information

Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory.

ABSTRACT: BACKGROUND:Non-small cell lung cancer (NSCLC) is one of the leading causes of death globally, and research into NSCLC has been accumulating steadily over several years. Drug repositioning is the current trend in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development process of drugs, as well as reducing side effects. RESULTS:This work integrates two approaches--machine learning algorithms and topological parameter-based classification--to develop a novel pipeline of drug repositioning to analyze four lung cancer microarray datasets, enriched biological processes, potential therapeutic drugs and targeted genes for NSCLC treatments. A total of 7 (8) and 11 (12) promising drugs (targeted genes) were discovered for treating early- and late-stage NSCLC, respectively. The effectiveness of these drugs is supported by the literature, experimentally determined in-vitro IC50 and clinical trials. This work provides better drug prediction accuracy than competitive research according to IC50 measurements. CONCLUSIONS:With the novel pipeline of drug repositioning, the discovery of enriched pathways and potential drugs related to NSCLC can provide insight into the key regulators of tumorigenesis and the treatment of NSCLC. Based on the verified effectiveness of the targeted drugs predicted by this pipeline, we suggest that our drug-finding pipeline is effective for repositioning drugs.

SUBMITTER: Huang CH

PROVIDER: S-EPMC4895785 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory.

Huang Chien-Hung CH Chang Peter Mu-Hsin PM Hsu Chia-Wei CW Huang Chi-Ying F CY Ng Ka-Lok KL

BMC bioinformatics 20160111

<h4>Background</h4>Non-small cell lung cancer (NSCLC) is one of the leading causes of death globally, and research into NSCLC has been accumulating steadily over several years. Drug repositioning is the current trend in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development process of drugs, as well as reducing side effects.<h4>Results</h4>This work integrates two approaches--machine learning algorithms and topological parameter-based c ...[more]

PMID: 26817825

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Project description:BackgroundDrug repositioning, also known as drug repurposing, defines new indications for existing drugs and can be used as an alternative to drug development. In recent years, the accumulation of large volumes of information related to drugs and diseases has led to the development of various computational approaches for drug repositioning. Although herbal medicines have had a great impact on current drug discovery, there are still a large number of herbal compounds that have no definite indications.ResultsIn the present study, we constructed a computational model to predict the unknown pharmacological effects of herbal compounds using machine learning techniques. Based on the assumption that similar diseases can be treated with similar drugs, we used four categories of drug-drug similarity (e.g., chemical structure, side-effects, gene ontology, and targets) and three categories of disease-disease similarity (e.g., phenotypes, human phenotype ontology, and gene ontology). Then, associations between drug and disease were predicted using the employed similarity features. The prediction models were constructed using classification algorithms, including logistic regression, random forest and support vector machine algorithms. Upon cross-validation, the random forest approach showed the best performance (AUC = 0.948) and also performed well in an external validation assessment using an unseen independent dataset (AUC = 0.828). Finally, the constructed model was applied to predict potential indications for existing drugs and herbal compounds. As a result, new indications for 20 existing drugs and 31 herbal compounds were predicted and validated using clinical trial data.ConclusionsThe predicted results were validated manually confirming the performance and underlying mechanisms - for example, irinotecan as a treatment for neuroblastoma. From the prediction, herbal compounds were considered to be drug candidates for related diseases which is important to be further developed. The proposed prediction model can contribute to drug discovery by suggesting drug candidates from herbal compounds which have potentials but few were studied.

Dataset Information

Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory.

Publications

Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory.

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