scholarly journals Enhanced Co-Expression Extrapolation (COXEN) Gene Selection Method for Building Anti-Cancer Drug Response Prediction Models

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1070 ◽  
Author(s):  
Yitan Zhu ◽  
Thomas Brettin ◽  
Yvonne A. Evrard ◽  
Fangfang Xia ◽  
Alexander Partin ◽  
...  
Keyword(s):  
Drug Response ◽  
Prediction Models ◽  
Gene Selection ◽  
Expression Patterns ◽  
Response Prediction ◽  
Cancer Drug ◽  
P Value ◽  
In Vitro Drug Screening ◽  
Multiple Drugs

The co-expression extrapolation (COXEN) method has been successfully used in multiple studies to select genes for predicting the response of tumor cells to a specific drug treatment. Here, we enhance the COXEN method to select genes that are predictive of the efficacies of multiple drugs for building general drug response prediction models that are not specific to a particular drug. The enhanced COXEN method first ranks the genes according to their prediction power for each individual drug and then takes a union of top predictive genes of all the drugs, among which the algorithm further selects genes whose co-expression patterns are well preserved between cancer cases for building prediction models. We apply the proposed method on benchmark in vitro drug screening datasets and compare the performance of prediction models built based on the genes selected by the enhanced COXEN method to that of models built on genes selected by the original COXEN method and randomly picked genes. Models built with the enhanced COXEN method always present a statistically significantly improved prediction performance (adjusted p-value ≤ 0.05). Our results demonstrate the enhanced COXEN method can dramatically increase the power of gene expression data for predicting drug response.

scholarly journals Enhanced co-expression extrapolation (COXEN) gene selection method for building anticancer drug response prediction models.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14073-e14073
Author(s):  
Yitan Zhu ◽  
Thomas S. Brettin ◽  
Fangfang Xia ◽  
Maulik Shukla ◽  
Alexander Partin ◽  
...  
Keyword(s):  
Prediction Model ◽  
Regression Model ◽  
Drug Response ◽  
Prediction Models ◽  
Gene Selection ◽  
Expression Patterns ◽  
Response Prediction ◽  
Precision Oncology ◽  
General Drug ◽  
Multiple Drugs

e14073 Background: Accurate prediction of tumor response to a drug treatment is of paramount importance for precision oncology. The co-expression extrapolation (COXEN) gene selection approach has been successfully used in multiple studies to select genes for predicting the response of tumor cells to a specific drug. Here, we enhance the original COXEN approach to select genes that are predictive of the efficacies of multiple drugs simultaneously for building general drug response prediction model. Methods: We implemented two methods to select predictive genes. The first method ranks the genes according to their prediction power for each individual drug and then takes a union of top predictive genes of all the drugs. The second method uses a linear regression model to evaluate the prediction power of a gene for all drugs while the drugs are one-hot encoded in the regression model. Among the predictive genes, we further select genes by evaluating the preservation of co-expression patterns between cancer cases with drug response data available and cancer cases for which drug response needs to be predicted, because the preservation of co-expression patterns indicates the similarity of genomic regulations between cancer cases. Results: To test the enhanced COXEN method, we used a lightGBM regression model to predict drug response based on the selected genes on two benchmark in vitro drug screening datasets. The table below compares the performance of prediction models built based on 200 genes selected by the enhanced COXEN method to that of models built on 200 genes randomly picked from the LINCS gene set, which includes 976 “landmark” genes well-representing cellular transcriptomic changes identified in the Library of Integrated Network-Based Cellular Signatures (LINCS) project. The enhanced COXEN approach selects genes better than random LINCS genes as demonstrated by the increased average coefficient of determination (R2) for predicting the area under the dose response curve through cross-validation. Pair-wise t-test indicates the improvement is statistically significant (p-value ≤ 0.05) on both datasets. Conclusions: Our result demonstrates the benefit of using an enhanced COXEN approach to select genes for building general drug response prediction model. [Table: see text]

scholarly journals Ensemble transfer learning for the prediction of anti-cancer drug response

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yitan Zhu ◽  
Thomas Brettin ◽  
Yvonne A. Evrard ◽  
Alexander Partin ◽  
Fangfang Xia ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Transfer Learning ◽  
Drug Response ◽  
Prediction Models ◽  
Response Prediction ◽  
Cancer Drug ◽  
Precision Oncology ◽  
Learning Framework ◽  
Prediction Algorithms ◽  
Anti Cancer

Abstract Transfer learning, which transfers patterns learned on a source dataset to a related target dataset for constructing prediction models, has been shown effective in many applications. In this paper, we investigate whether transfer learning can be used to improve the performance of anti-cancer drug response prediction models. Previous transfer learning studies for drug response prediction focused on building models to predict the response of tumor cells to a specific drug treatment. We target the more challenging task of building general prediction models that can make predictions for both new tumor cells and new drugs. Uniquely, we investigate the power of transfer learning for three drug response prediction applications including drug repurposing, precision oncology, and new drug development, through different data partition schemes in cross-validation. We extend the classic transfer learning framework through ensemble and demonstrate its general utility with three representative prediction algorithms including a gradient boosting model and two deep neural networks. The ensemble transfer learning framework is tested on benchmark in vitro drug screening datasets. The results demonstrate that our framework broadly improves the prediction performance in all three drug response prediction applications with all three prediction algorithms.

scholarly journals Clinical Drug Response Prediction by Using a Lq Penalized Network-Constrained Logistic Regression Method

2018 ◽  
Vol 51 (5) ◽  
pp. 2073-2084 ◽  
Author(s):  
Hai-Hui Huang ◽  
Jing-Guo Dai ◽  
Yong Liang
Keyword(s):  
Gene Expression ◽  
Logistic Regression ◽  
Personalized Medicine ◽  
Gene Expression Data ◽  
Drug Response ◽  
Prediction Models ◽  
Response Prediction ◽  
Expression Data

Background/Aims: One of the most important impacts of personalized medicine is the connection between patients’ genotypes and their drug responses. Despite a series of studies exploring this relationship, the predictive ability of such analyses still needs to be strengthened. Methods: Here we present the Lq penalized network-constrained logistic regression (Lq-NLR) method to meet this need, in which the predictors are integrated into the gene expression data and biological network knowledge and are combined with a more aggressive penalty function. Response prediction models for two cancer targeting drugs (erlotinib and sorafenib) were developed from gene expression data and IC50 values from a large panel of cancer cell lines by utilizing the proposed approach. Then the drug responders were tested with the baseline tumor gene expression data, yielding an in vivo drug sensitivity prediction. Results: These results demonstrated the high effectiveness of this approach. One of the best results achieved by our method was a correlation of 0.841 between the cell line in vitro drug response and patient’s in vivo drug response. We then applied these two drug prediction models to develop a personalized medicine approach in which the subsequent treatment depends on each patient’s gene-expression profile. Conclusion: The proposed method is much better than the existing approach and can capture a more accurate reflection of the relationship between genotypes and phenotypes.

AttDRP: Attention Mechanism-based Model for Anti-Cancer Drug Response Prediction

2021 ◽  
Vol 48 (6) ◽  
pp. 713-722
Author(s):  
Jonghwan Choi ◽  
Sangmin Seo ◽  
Sanghyun Park
Keyword(s):  
Drug Response ◽  
Response Prediction ◽  
Attention Mechanism ◽  
Cancer Drug ◽  
Anti Cancer

scholarly journals FORESEE: a tool for the systematic comparison of translational drug response modeling pipelines

2018 ◽  
Author(s):  
Lisa-Katrin Turnhoff ◽  
Ali Hadizadeh Esfahani ◽  
Maryam Montazeri ◽  
Nina Kusch ◽  
Andreas Schuppert
Keyword(s):  
Drug Response ◽  
Drug Efficacy ◽  
Response Prediction ◽  
R Package ◽  
Supplementary Information ◽  
Supplementary File ◽  
Data Sets ◽  
Training Algorithms ◽  
Model Training

Translational models that utilize omics data generated in in vitro studies to predict the drug efficacy of anti-cancer compounds in patients are highly distinct, which complicates the benchmarking process for new computational approaches. In reaction to this, we introduce the uniFied translatiOnal dRug rESponsE prEdiction platform FORESEE, an open-source R-package. FORESEE not only provides a uniform data format for public cell line and patient data sets, but also establishes a standardized environment for drug response prediction pipelines, incorporating various state-of-the-art preprocessing methods, model training algorithms and validation techniques. The modular implementation of individual elements of the pipeline facilitates a straightforward development of combinatorial models, which can be used to re-evaluate and improve already existing pipelines as well as to develop new ones. Availability and Implementation: FORESEE is licensed under GNU General Public License v3.0 and available at https://github.com/JRC-COMBINE/FORESEE . Supplementary Information: Supplementary Files 1 and 2 provide detailed descriptions of the pipeline and the data preparation process, while Supplementary File 3 presents basic use cases of the package. Contact: [email protected]

scholarly journals MOLI: multi-omics late integration with deep neural networks for drug response prediction

2019 ◽  
Vol 35 (14) ◽  
pp. i501-i509 ◽  
Author(s):  
Hossein Sharifi-Noghabi ◽  
Olga Zolotareva ◽  
Colin C Collins ◽  
Martin Ester
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Prediction Accuracy ◽  
Drug Response ◽  
Deep Neural Networks ◽  
Response Prediction ◽  
Supplementary Information ◽  
Precision Oncology

Abstract Motivation Historically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance. Results We propose MOLI, a multi-omics late integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding sub-networks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each other and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI’s performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI’s high predictive power suggests it may have utility in precision oncology. Availability and implementation https://github.com/hosseinshn/MOLI. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Computational modeling of methionine cycle-based metabolism and DNA methylation and the implications for anti-cancer drug response prediction

Oncotarget ◽  
2018 ◽  
Vol 9 (32) ◽  
pp. 22546-22558 ◽  
Author(s):  
Mengying Zhang ◽  
Christian Saad ◽  
Lien Le ◽  
Kathrin Halfter ◽  
Bernhard Bauer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Computational Modeling ◽  
Drug Response ◽  
Response Prediction ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Methionine Cycle

Deep learning for drug response prediction in cancer

2020 ◽  
Author(s):  
Delora Baptista ◽  
Pedro G Ferreira ◽  
Miguel Rocha
Keyword(s):  
Deep Learning ◽  
Cell Lines ◽  
Cancer Cell ◽  
High Throughput Screening ◽  
Drug Response ◽  
Prediction Models ◽  
Response Prediction ◽  
Cancer Cell Lines ◽  
Cancer Treatments ◽  
Novel Drugs

Abstract Predicting the sensitivity of tumors to specific anti-cancer treatments is a challenge of paramount importance for precision medicine. Machine learning(ML) algorithms can be trained on high-throughput screening data to develop models that are able to predict the response of cancer cell lines and patients to novel drugs or drug combinations. Deep learning (DL) refers to a distinct class of ML algorithms that have achieved top-level performance in a variety of fields, including drug discovery. These types of models have unique characteristics that may make them more suitable for the complex task of modeling drug response based on both biological and chemical data, but the application of DL to drug response prediction has been unexplored until very recently. The few studies that have been published have shown promising results, and the use of DL for drug response prediction is beginning to attract greater interest from researchers in the field. In this article, we critically review recently published studies that have employed DL methods to predict drug response in cancer cell lines. We also provide a brief description of DL and the main types of architectures that have been used in these studies. Additionally, we present a selection of publicly available drug screening data resources that can be used to develop drug response prediction models. Finally, we also address the limitations of these approaches and provide a discussion on possible paths for further improvement. Contact:[email protected]

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