FG-BERT: a generalized and self-supervised functional group-based molecular representation learning framework for properties prediction.

Artificial intelligence-based molecular property prediction plays a key role in molecular design such as bioactive molecules and functional materials. In this study, we propose a self-supervised pretraining deep learning (DL) framework, called functional group bidirectional encoder representations from transformers (FG-BERT), pertained based on ~1.45 million unlabeled drug-like molecules, to learn meaningful representation of molecules from function groups. The pretrained FG-BERT framework can be fine-tuned to predict molecular properties. Compared to state-of-the-art (SOTA) machine learning and DL methods, we demonstrate the high performance of FG-BERT in evaluating molecular properties in tasks involving physical chemistry, biophysics and physiology across 44 benchmark datasets. In addition, FG-BERT utilizes attention mechanisms to focus on FG features that are critical to the target properties, thereby providing excellent interpretability for downstream training tasks. Collectively, FG-BERT does not require any artificially crafted features as input and has excellent interpretability, providing an out-of-the-box framework for developing SOTA models for a variety of molecule (especially for drug) discovery tasks.

MMSyn: A New Multimodal Deep Learning Framework for Enhanced Prediction of Synergistic Drug Combinations.

Combination therapy is a promising strategy for the successful treatment of cancer. The large number of possible combinations, however, mean that it is laborious and expensive to screen for synergistic drug combinations in vitro. Nevertheless, because of the availability of high-throughput screening data and advances in computational techniques, deep learning (DL) can be a useful tool for the prediction of synergistic drug combinations. In this study, we proposed a multimodal DL framework, MMSyn, for the prediction of synergistic drug combinations. First, features embedded in the drug molecules were extracted: structure, fingerprint, and string encoding. Then, gene expression data, DNA copy number, and pathway activity were used to describe cancer cell lines. Finally, these processed features were integrated using an attention mechanism and an interaction module and then input into a multilayer perceptron to predict drug synergy. Experimental results showed that our method outperformed five state-of-the-art DL methods and three traditional machine learning models for drug combination prediction. We verified that MMSyn achieved superior performance in stratified cross-validation settings using both the drug combination and cell line data. Moreover, we performed a set of ablation experiments to illustrate the effectiveness of each component and the efficacy of our model. In addition, our visual representation and case studies further confirmed the effectiveness of our model. All results showed that MMSyn can be used as a powerful tool for the prediction of synergistic drug combinations.

Large-scale comparison of machine learning methods for profiling prediction of kinase inhibitors.

Conventional machine learning (ML) and deep learning (DL) play a key role in the selectivity prediction of kinase inhibitors. A number of models based on available datasets can be used to predict the kinase profile of compounds, but there is still controversy about the advantages and disadvantages of ML and DL for such tasks. In this study, we constructed a comprehensive benchmark dataset of kinase inhibitors, involving in 141,086 unique compounds and 216,823 well-defined bioassay data points for 354 kinases. We then systematically compared the performance of 12 ML and DL methods on the kinase profiling prediction task. Extensive experimental results reveal that (1) Descriptor-based ML models generally slightly outperform fingerprint-based ML models in terms of predictive performance. RF as an ensemble learning approach displays the overall best predictive performance. (2) Single-task graph-based DL models are generally inferior to conventional descriptor- and fingerprint-based ML models, however, the corresponding multi-task models generally improves the average accuracy of kinase profile prediction. For example, the multi-task FP-GNN model outperforms the conventional descriptor- and fingerprint-based ML models with an average AUC of 0.807. (3) Fusion models based on voting and stacking methods can further improve the performance of the kinase profiling prediction task, specifically, RF::AtomPairs + FP2 + RDKitDes fusion model performs best with the highest average AUC value of 0.825 on the test sets. These findings provide useful information for guiding choices of the ML and DL methods for the kinase profiling prediction tasks. Finally, an online platform called KIPP ( https://kipp.idruglab.cn ) and python software are developed based on the best models to support the kinase profiling prediction, as well as various kinase inhibitor identification tasks including virtual screening, compound repositioning and target fishing.

DeepCancerMap: A versatile deep learning platform for target- and cell-based anticancer drug discovery.

Discovering new anticancer drugs has been widely concerned and remains an open challenge. Target- and phenotypic-based experimental screening represent two mainstream anticancer drug discovery methods, which suffer from time-consuming, labor-intensive, and high experimental costs. In this study, we collected 485,900 compounds involving in 3,919,974 bioactivity records against 426 anticancer targets and 346 cancer cell lines from academic literature, as well as 60 tumor cell lines from NCI-60 panel. A total of 832 classification models (426 target- and 406 cell-based predictive models) were then constructed to predict the inhibitory activity of compounds against targets and tumor cell lines using FP-GNN deep learning method. Compared to the classical machine learning and deep learning methods, the FP-GNN models achieve considerable overall predictive performance, with the highest AUC values of 0.91, 0.88, 0.91 for the test sets of targets, academia-sourced and NCI-60 cancer cell lines, respectively. A user-friendly webserver called DeepCancerMap and its local version were developed based on these high-quality models, enabling users to perform anticancer drug discovery-related tasks including large-scale virtual screening, profiling prediction of anticancer agents, target fishing, and drug repositioning. We anticipate this platform to accelerate the discovery of anticancer drugs in the field. DeepCancerMap is freely available at https://deepcancermap.idruglab.cn.