Dataset Information

TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations.

ABSTRACT: Drug combinations have demonstrated great potential in cancer treatments. They alleviate drug resistance and improve therapeutic efficacy. The fast-growing number of anti-cancer drugs has caused the experimental investigation of all drug combinations to become costly and time-consuming. Computational techniques can improve the efficiency of drug combination screening. Despite recent advances in applying machine learning to synergistic drug combination prediction, several challenges remain. First, the performance of existing methods is suboptimal. There is still much space for improvement. Second, biological knowledge has not been fully incorporated into the model. Finally, many models are lack interpretability, limiting their clinical applications. To address these challenges, we have developed a knowledge-enabled and self-attention transformer boosted deep learning model, TranSynergy, which improves the performance and interpretability of synergistic drug combination prediction. TranSynergy is designed so that the cellular effect of drug actions can be explicitly modeled through cell-line gene dependency, gene-gene interaction, and genome-wide drug-target interaction. A novel Shapley Additive Gene Set Enrichment Analysis (SA-GSEA) method has been developed to deconvolute genes that contribute to the synergistic drug combination and improve model interpretability. Extensive benchmark studies demonstrate that TranSynergy outperforms the state-of-the-art method, suggesting the potential of mechanism-driven machine learning. Novel pathways that are associated with the synergistic combinations are revealed and supported by experimental evidences. They may provide new insights into identifying biomarkers for precision medicine and discovering new anti-cancer therapies. Several new synergistic drug combinations have been predicted with high confidence for ovarian cancer which has few treatment options. The code is available at https://github.com/qiaoliuhub/drug_combination.

SUBMITTER: Liu Q

PROVIDER: S-EPMC7906476 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations.

Liu Qiao Q Xie Lei L

PLoS computational biology 20210212 2

Drug combinations have demonstrated great potential in cancer treatments. They alleviate drug resistance and improve therapeutic efficacy. The fast-growing number of anti-cancer drugs has caused the experimental investigation of all drug combinations to become costly and time-consuming. Computational techniques can improve the efficiency of drug combination screening. Despite recent advances in applying machine learning to synergistic drug combination prediction, several challenges remain. First ...[more]

PMID: 33577560

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Project description:The effective decoding of movement from non-invasive electroencephalography (EEG) is essential for informing several therapeutic interventions, from neurorehabilitation robots to neural prosthetics. Deep neural networks are most suitable for decoding real-time data but their use in EEG is hindered by the gross classes of motor tasks in the currently available datasets, which are solvable even with network architectures that do not require specialized design considerations. Moreover, the weak association with the underlying neurophysiology limits the generalizability of modern networks for EEG inference. Here, we present a neurophysiologically interpretable 3-dimensional convolutional neural network (3D-CNN) that captured the spatiotemporal dependencies in brain areas that get co-activated during movement. The 3D-CNN received topography-preserving EEG inputs, and predicted complex components of hand movements performed on a plane using a back-drivable rehabilitation robot, namely (a) the reaction time (RT) for responding to stimulus (slow or fast), (b) the mode of movement (active or passive, depending on whether there was an assistive force provided by the apparatus), and (c) the orthogonal directions of the movement (left, right, up, or down). We validated the 3D-CNN on a new dataset that we acquired from an in-house motor experiment, where it achieved average leave-one-subject-out test accuracies of 79.81%, 81.23%, and 82.00% for RT, active vs. passive, and direction classifications, respectively. Our proposed method outperformed the modern 2D-CNN architecture by a range of 1.1% to 6.74% depending on the classification task. Further, we identified the EEG sensors and time segments crucial to the classification decisions of the network, which aligned well with the current neurophysiological knowledge on brain activity in motor planning and execution tasks. Our results demonstrate the importance of biological relevance in networks for an accurate decoding of EEG, suggesting that the real-time classification of other complex brain activities may now be within our reach.

Dataset Information

TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations.

Publications

TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations.

Similar Datasets

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