Dataset Information

Anticancer Drug Response Prediction in Cell Lines Using Weighted Graph Regularized Matrix Factorization.

ABSTRACT: Precision medicine has become a novel and rising concept, which depends much on the identification of individual genomic signatures for different patients. The cancer cell lines could reflect the "omic" diversity of primary tumors, based on which many works have been carried out to study the cancer biology and drug discovery both in experimental and computational aspects. In this work, we presented a novel method to utilize weighted graph regularized matrix factorization (WGRMF) for inferring anticancer drug response in cell lines. We constructed a p-nearest neighbor graph to sparsify drug similarity matrix and cell line similarity matrix, respectively. Using the sparsified matrices in the graph regularization terms, we performed matrix factorization to generate the latent matrices for drug and cell line. The graph regularization terms including neighbor information could help to exclude the noisy ingredient and improve the prediction accuracy. The 10-fold cross-validation was implemented, and the Pearson correlation coefficient (PCC), root-mean-square error (RMSE), PCCsr, and RMSEsr averaged over all drugs were calculated to evaluate the performance of WGRMF. The results on the Genomics of Drug Sensitivity in Cancer (GDSC) dataset are 0.64 ± 0.16, 1.37 ± 0.35, 0.73 ± 0.14, and 1.71 ± 0.44 for PCC, RMSE, PCCsr, and RMSEsr in turn. And for the Cancer Cell Line Encyclopedia (CCLE) dataset, WGRMF got results of 0.72 ± 0.09, 0.56 ± 0.19, 0.79 ± 0.07, and 0.69 ± 0.19, respectively. The results showed the superiority of WGRMF compared with previous methods. Besides, based on the prediction results using the GDSC dataset, three types of case studies were carried out. The results from both cross-validation and case studies have shown the effectiveness of WGRMF on the prediction of drug response in cell lines.

SUBMITTER: Guan NN

PROVIDER: S-EPMC6610642 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Anticancer Drug Response Prediction in Cell Lines Using Weighted Graph Regularized Matrix Factorization.

Guan Na-Na NN Zhao Yan Y Wang Chun-Chun CC Li Jian-Qiang JQ Chen Xing X Piao Xue X

Molecular therapy. Nucleic acids 20190604

Precision medicine has become a novel and rising concept, which depends much on the identification of individual genomic signatures for different patients. The cancer cell lines could reflect the "omic" diversity of primary tumors, based on which many works have been carried out to study the cancer biology and drug discovery both in experimental and computational aspects. In this work, we presented a novel method to utilize weighted graph regularized matrix factorization (WGRMF) for inferring an ...[more]

PMID: 31265947

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Project description:BackgroundHuman cancer cell lines are used in research to study the biology of cancer and to test cancer treatments. Recently there are already some large panels of several hundred human cancer cell lines which are characterized with genomic and pharmacological data. The ability to predict drug responses using these pharmacogenomics data can facilitate the development of precision cancer medicines. Although several methods have been developed to address the drug response prediction, there are many challenges in obtaining accurate prediction.MethodsBased on the fact that similar cell lines and similar drugs exhibit similar drug responses, we adopted a similarity-regularized matrix factorization (SRMF) method to predict anticancer drug responses of cell lines using chemical structures of drugs and baseline gene expression levels in cell lines. Specifically, chemical structural similarity of drugs and gene expression profile similarity of cell lines were considered as regularization terms, which were incorporated to the drug response matrix factorization model.ResultsWe first demonstrated the effectiveness of SRMF using a set of simulation data and compared it with two typical similarity-based methods. Furthermore, we applied it to the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) datasets, and performance of SRMF exceeds three state-of-the-art methods. We also applied SRMF to estimate the missing drug response values in the GDSC dataset. Even though SRMF does not specifically model mutation information, it could correctly predict drug-cancer gene associations that are consistent with existing data, and identify novel drug-cancer gene associations that are not found in existing data as well. SRMF can also aid in drug repositioning. The newly predicted drug responses of GDSC dataset suggest that mTOR inhibitor rapamycin was sensitive to non-small cell lung cancer (NSCLC), and expression of AK1RC3 and HINT1 may be adjunct markers of cell line sensitivity to rapamycin.ConclusionsOur analysis showed that the proposed data integration method is able to improve the accuracy of prediction of anticancer drug responses in cell lines, and can identify consistent and novel drug-cancer gene associations compared to existing data as well as aid in drug repositioning.

Project description:BackgroundBecause drug-drug interactions (DDIs) may cause adverse drug reactions or contribute to complex-disease treatments, it is important to identify DDIs before multiple-drug medications are prescribed. As the alternative of high-cost experimental identifications, computational approaches provide a much cheaper screening for potential DDIs on a large scale manner. Nevertheless, most of them only predict whether or not one drug interacts with another, but neglect their enhancive (positive) and depressive (negative) changes of pharmacological effects. Moreover, these comprehensive DDIs do not occur at random, but exhibit a weakly balanced relationship (a structural property when considering the DDI network), which would help understand how high-order DDIs work.ResultsThis work exploits the intrinsically structural relationship to solve two tasks, including drug community detection as well as comprehensive DDI prediction in the cold-start scenario. Accordingly, we first design a balance regularized semi-nonnegative matrix factorization (BRSNMF) to partition the drugs into communities. Then, to predict enhancive and degressive DDIs in the cold-start scenario, we develop a BRSNMF-based predictive approach, which technically leverages drug-binding proteins (DBP) as features to associate new drugs (having no known DDI) with other drugs (having known DDIs). Our experiments demonstrate that BRSNMF can generate the drug communities, which exhibit more reasonable sizes, the property of weak balance as well as pharmacological significances. Moreover, they demonstrate the superiority of DBP features and the inspiring ability of the BRSNMF-based predictive approach on comprehensive DDI prediction with 94% accuracy among top-50 predicted enhancive and 86% accuracy among bottom-50 predicted degressive DDIs.ConclusionsOwing to the regularization of the weak balance property of the comprehensive DDI network into semi-nonnegative matrix factorization, our proposed BRSNMF is able to not only generate better drug communities but also provide an inspiring comprehensive DDI prediction in the cold-start scenario.

Dataset Information

Anticancer Drug Response Prediction in Cell Lines Using Weighted Graph Regularized Matrix Factorization.

Publications

Anticancer Drug Response Prediction in Cell Lines Using Weighted Graph Regularized Matrix Factorization.

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