Search for: All records

Combination therapy has gained popularity in cancer treatment as it enhances the treatment efficacy and overcomes drug resistance. Although machine learning (ML) techniques have become an indispensable tool for discovering new drug combinations, the data on drug combination therapy currently available may be insufficient to build high-precision models. We developed a data augmentation protocol to unbiasedly scale up the existing anti-cancer drug synergy dataset. Using a new drug similarity metric, we augmented the synergy data by substituting a compound in a drug combination instance with another molecule that exhibits highly similar pharmacological effects. Using this protocol, we were able to upscale the AZ-DREAM Challenges dataset from 8798 to 6,016,697 drug combinations. Comprehensive performance evaluations show that ML models trained on the augmented data consistently achieve higher accuracy than those trained solely on the original dataset. Our data augmentation protocol provides a systematic and unbiased approach to generating more diverse and larger-scale drug combination datasets, enabling the development of more precise and effective ML models. The protocol presented in this study could serve as a foundation for future research aimed at discovering novel and effective drug combinations for cancer treatment.

 

Genomic profiles of cancer cells provide valuable information on genetic alterations in cancer. Several recent studies employed these data to predict the response of cancer cell lines to drug treatment. Nonetheless, due to the multifactorial phenotypes and intricate mechanisms of cancer, the accurate prediction of the effect of pharmacotherapy on a specific cell line based on the genetic information alone is problematic. Emphasizing on the system-level complexity of cancer, we devised a procedure to integrate multiple heterogeneous data, including biological networks, genomics, inhibitor profiling, and gene-disease associations, into a unified graph structure. In order to construct compact, yet information-rich cancer-specific networks, we developed a novel graph reduction algorithm. Driven by not only the topological information, but also the biological knowledge, the graph reduction increases the feature-only entropy while preserving the valuable graph-feature information. Subsequent comparative benchmarking simulations employing a tissue level cross-validation protocol demonstrate that the accuracy of a graph-based predictor of the drug efficacy is 0.68, which is notably higher than those measured for more traditional, matrix-based techniques on the same data. Overall, the non-Euclidean representation of the cancer-specific data improves the performance of machine learning to predict the response of cancer to pharmacotherapy. The generated data are freely available to the academic community athttps://osf.io/dzx7b/.

 

Abstract Traditional techniques to identify macromolecular targets for drugs utilize solely the information on a query drug and a putative target. Nonetheless, the mechanisms of action of many drugs depend not only on their binding affinity toward a single protein, but also on the signal transduction through cascades of molecular interactions leading to certain phenotypes. Although using protein-protein interaction networks and drug-perturbed gene expression profiles can facilitate system-level investigations of drug-target interactions, utilizing such large and heterogeneous data poses notable challenges. To improve the state-of-the-art in drug target identification, we developed GraphDTI, a robust machine learning framework integrating the molecular-level information on drugs, proteins, and binding sites with the system-level information on gene expression and protein-protein interactions. In order to properly evaluate the performance of GraphDTI, we compiled a high-quality benchmarking dataset and devised a new cluster-based cross-validation protocol. Encouragingly, GraphDTI not only yields an AUC of 0.996 against the validation dataset, but it also generalizes well to unseen data with an AUC of 0.939, significantly outperforming other predictors. Finally, selected examples of identified drugtarget interactions are validated against the biomedical literature. Numerous applications of GraphDTI include the investigation of drug polypharmacological effects, side effects through offtarget binding, and repositioning opportunities. 

Computer scientists and programmers face the difficultly of improving the scalability of their applications while using conventional programming techniques only. As a base-line hypothesis of this paper we assume that an advanced runtime system can be used to take full advantage of the available parallel resources of a machine in order to achieve the highest parallelism possible. In this paper we present the capabilities of HPX - a distributed runtime system for parallel applications of any scale - to achieve the best possible scalability through asynchronous task execution [1]. OP2 is an active library which provides a framework for the parallel execution for unstructured grid applications on different multi-core/many-core hardware architectures [2]. OP2 generates code which uses OpenMP for loop parallelization within an application code for both single-threaded and multi-threaded machines. In this work we modify the OP2 code generator to target HPX instead of OpenMP, i.e. port the parallel simulation backend of OP2 to utilize HPX. We compare the performance results of the different parallelization methods using HPX and OpenMP for loop parallelization within the Airfoil application. The results of strong scaling and weak scaling tests for the Airfoil application on one node with up to 32 threads are presented. Using HPX for parallelization of OP2 gives an improvement in performance by 5%-21%. By modifying the OP2 code generator to use HPX's parallel algorithms, we observe scaling improvements by about 5% as compared to OpenMP. To fully exploit the potential of HPX, we adapted the OP2 API to expose a future and dataflow based programming model and applied this technique for parallelizing the same Airfoil application. We show that the dataflow oriented programming model, which automatically creates an execution tree representing the algorithmic data dependencies of our application, improves the overall scaling results by about 21% compared to OpenMP. Our results show the advantage of using the asynchronous programming model implemented by HPX. 

One of the major challenges in parallelization is the difficulty of improving application scalability with conventional techniques. HPX provides efficient scalable parallelism by significantly reducing node starvation and effective latencies while controlling the overheads. In this paper, we present a new highly scalable parallel distributed N-Body application using a future-based algorithm, which is implemented with HPX. The main difference between this algorithm and prior art is that a future-based request buffer is used between different nodes and along each spatial direction to send/receive data to/from the remote nodes, which helps removing synchronization barriers. HPX provides an asynchronous programming model which results in improving the parallel performance. The results of using HPX for parallelizing Octree construction on one node and the force computation on the distributed nodes show the scalability improvement on an average by about 45% compared to an equivalent OpenMP implementation and 28% compared to a hybrid implementation (MPI+OpenMP) [1] respectively for one billion particles running on up to 128 nodes with 20 cores per each.