Perceiver CPI: a nested cross-attention network for compound-protein interaction prediction.

MOTIVATION: Compound-protein interaction (CPI) plays an essential role in drug discovery and is performed via expensive molecular docking simulations. Many artificial intelligence-based approaches have been proposed in this regard. Recently, two types of models have accomplished promising results in exploiting molecular information: graph convolutional neural networks that construct a learned molecular representation from a graph structure (atoms and bonds), and neural networks that can be applied to compute on descriptors or fingerprints of molecules. However, the superiority of one method over the other is yet to be determined. Modern studies have endeavored to aggregate information that is extracted from compounds and proteins to form the CPI task. Nonetheless, these approaches have used a simple concatenation to combine them, which cannot fully capture the interaction between such information. RESULTS: We propose the Perceiver CPI network, which adopts a cross-attention mechanism to improve the learning ability of the representation of drug and target interactions and exploits the rich information obtained from extended-connectivity fingerprints to improve the performance. We evaluated Perceiver CPI on three main datasets, Davis, KIBA and Metz, to compare the performance of our proposed model with that of state-of-the-art methods. The proposed method achieved satisfactory performance and exhibited significant improvements over previous approaches in all experiments. AVAILABILITY AND IMPLEMENTATION: Perceiver CPI is available at https://github.com/dmis-lab/PerceiverCPI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Predicting mechanism of action of novel compounds using compound structure and transcriptomic signature coembedding.

MOTIVATION: Identifying mechanism of actions (MoA) of novel compounds is crucial in drug discovery. Careful understanding of MoA can avoid potential side effects of drug candidates. Efforts have been made to identify MoA using the transcriptomic signatures induced by compounds. However, these approaches fail to reveal MoAs in the absence of actual compound signatures. RESULTS: We present MoAble, which predicts MoAs without requiring compound signatures. We train a deep learning-based coembedding model to map compound signatures and compound structure into the same embedding space. The model generates low-dimensional compound signature representation from the compound structures. To predict MoAs, pathway enrichment analysis is performed based on the connectivity between embedding vectors of compounds and those of genetic perturbation. Results show that MoAble is comparable to the methods that use actual compound signatures. We demonstrate that MoAble can be used to reveal MoAs of novel compounds without measuring compound signatures with the same prediction accuracy as that with measuring them. AVAILABILITY AND IMPLEMENTATION: MoAble is available at https://github.com/dmis-lab/moable. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.