Ensembled machine learning framework for drug sensitivity prediction.

Drug sensitivity prediction is one of the critical tasks involved in drug designing and discovery. Recently several online databases and consortiums have contributed to providing open access to pharmacogenomic data. These databases have helped in developing computational approaches for drug sensitivity prediction. Cancer is a complex disease involving the heterogeneous behaviour of same tumour-type patients towards the same kind of drug therapy. Several methods have been proposed in the literature to predict drug sensitivity. However, these methods are not efficient enough to predict drug sensitivity. The present study has proposed an ensemble learning framework for drug-response prediction using a modified rotation forest. The proposed framework is further compared with three state-of-the-art algorithms and two baseline methods using Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) drug screens. The authors have also predicted missing drug response values in the data set using the proposed approach. The proposed approach outperforms other counterparts even though gene mutation data is not incorporated while designing the approach. An average mean square error of 3.14 and 0.404 is achieved using GDSC and CCLE drug screens, respectively. The obtained results show that the proposed framework has considerable potential to improve anti-cancer drug response prediction.

C-HMOSHSSA: Gene selection for cancer classification using multi-objective meta-heuristic and machine learning methods.

BACKGROUND AND OBJECTIVE: Over the last two decades, DNA microarray technology has emerged as a powerful tool for early cancer detection and prevention. It helps to provide a detailed overview of disease complex microenvironment. Moreover, online availability of thousands of gene expression assays made microarray data classification an active research area. A common goal is to find a minimum subset of genes and maximizing the classification accuracy. METHODS: In pursuit of a similar objective, we have proposed framework (C-HMOSHSSA) for gene selection using multi-objective spotted hyena optimizer (MOSHO) and salp swarm algorithm (SSA). The real-life optimization problems with more than one objective usually face the challenge to maintain convergence and diversity. Salp Swarm Algorithm (SSA) maintains diversity but, suffers from the overhead of maintaining the necessary information. On the other hand, the calculation of MOSHO requires low computational efforts hence is used for maintaining the necessary information. Therefore, the proposed algorithm is a hybrid algorithm that utilizes the features of both SSA and MOSHO to facilitate its exploration and exploitation capability. RESULTS: Four different classifiers are trained on seven high-dimensional datasets using a subset of features (genes), which are obtained after applying the proposed hybrid gene selection algorithm. The results show that the proposed technique significantly outperforms existing state-of-the-art techniques. CONCLUSION: It is also shown that the new sets of informative and biologically relevant genes are successfully identified by the proposed technique. The proposed approach can also be applied to other problem domains of interest which involve feature selection.

BE-DTI': Ensemble framework for drug target interaction prediction using dimensionality reduction and active learning.

BACKGROUND AND OBJECTIVE: Drug-target interaction prediction plays an intrinsic role in the drug discovery process. Prediction of novel drugs and targets helps in identifying optimal drug therapies for various stringent diseases. Computational prediction of drug-target interactions can help to identify potential drug-target pairs and speed-up the process of drug repositioning. In our present, work we have focused on machine learning algorithms for predicting drug-target interactions from the pool of existing drug-target data. The key idea is to train the classifier using existing DTI so as to predict new or unknown DTI. However, there are various challenges such as class imbalance and high dimensional nature of data that need to be addressed before developing optimal drug-target interaction model. METHODS: In this paper, we propose a bagging based ensemble framework named BE-DTI' for drug-target interaction prediction using dimensionality reduction and active learning to deal with class-imbalanced data. Active learning helps to improve under-sampling bagging based ensembles. Dimensionality reduction is used to deal with high dimensional data. RESULTS: Results show that the proposed technique outperforms the other five competing methods in 10-fold cross-validation experiments in terms of AUC=0.927, Sensitivity=0.886, Specificity=0.864, and G-mean=0.874. CONCLUSION: Missing interactions and new interactions are predicted using the proposed framework. Some of the known interactions are removed from the original dataset and their interactions are recalculated to check the accuracy of the proposed framework. Moreover, validation of the proposed approach is performed using the external dataset. All these results show that structurally similar drugs tend to interact with similar targets.

An integrated framework for identification of effective and synergistic anti-cancer drug combinations.

Combination drug therapy is considered a better treatment option for various diseases, such as cancer, HIV, hypertension, and infections as compared to targeted drug therapies. Combination or synergism helps to overcome drug resistance, reduction in drug toxicity and dosage. Considering the complexity and heterogeneity among cancer types, drug combination provides promising treatment strategy. Increase in drug combination data raises a challenge for developing a computational approach that can effectively predict drugs synergism. There is a need to model the combination drug screening data to predict new synergistic drug combinations for successful cancer treatment. In such a scenario, machine learning approaches can be used to alleviate the process of drugs synergy prediction. Experimental data from a single-agent or multi-agent drug screens provides feature data for model training. On the contrary, identification of effective drug combination using clinical trials is a time consuming and resource intensive task. This paper attempts to address the aforementioned challenges by developing a computational approach to effectively predict drug synergy. Single-drug efficacy is used for predicting drug synergism. Our approach obviates the need to understand the underlying drug mechanism to predict drug combination synergy. For this purpose, nine machine learning algorithms are trained. It is observed that the Random forest models, in comparison to other models, have shown significant performance. The K -fold cross-validation is performed to evaluate the robustness of the best predictive model. The proposed approach is applied to mutant-BRAF melanoma and further validated using melanoma cell-lines from AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge dataset.