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.

Project description:BackgroundIn recent years, mobile-based interventions have received more attention as an alternative to on-site obesity management. Despite increased mobile interventions for obesity, there are lost opportunities to achieve better outcomes due to the lack of a predictive model using current existing longitudinal and cross-sectional health data. Noom (Noom Inc) is a mobile app that provides various lifestyle-related logs including food logging, exercise logging, and weight logging.ObjectiveThe aim of this study was to develop a weight change predictive model using an interpretable artificial intelligence algorithm for mobile-based interventions and to explore contributing factors to weight loss.MethodsLifelog mobile app (Noom) user data of individuals who used the weight loss program for 16 weeks in the United States were used to develop an interpretable recurrent neural network algorithm for weight prediction that considers both time-variant and time-fixed variables. From a total of 93,696 users in the coaching program, we excluded users who did not take part in the 16-week weight loss program or who were not overweight or obese or had not entered weight or meal records for the entire 16-week program. This interpretable model was trained and validated with 5-fold cross-validation (training set: 70%; testing: 30%) using the lifelog data. Mean absolute percentage error between actual weight loss and predicted weight was used to measure model performance. To better understand the behavior factors contributing to weight loss or gain, we calculated contribution coefficients in test sets.ResultsA total of 17,867 users' data were included in the analysis. The overall mean absolute percentage error of the model was 3.50%, and the error of the model declined from 3.78% to 3.45% by the end of the program. The time-level attention weighting was shown to be equally distributed at 0.0625 each week, but this gradually decreased (from 0.0626 to 0.0624) as it approached 16 weeks. Factors such as usage pattern, weight input frequency, meal input adherence, exercise, and sharp decreases in weight trajectories had negative contribution coefficients of -0.021, -0.032, -0.015, and -0.066, respectively. For time-fixed variables, being male had a contribution coefficient of -0.091.ConclusionsAn interpretable algorithm, with both time-variant and time-fixed data, was used to precisely predict weight loss while preserving model transparency. This week-to-week prediction model is expected to improve weight loss and provide a global explanation of contributing factors, leading to better outcomes.

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.

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