Deep learning for drug repurposing: methods, databases, and applications

Drug development is time-consuming and expensive. Repurposing existing drugs for new therapies is an attractive solution that accelerates drug development at reduced experimental costs, specifically for Coronavirus Disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensively obtaining and productively integrating available knowledge and big biomedical data to effectively advance deep learning models is still challenging for drug repurposing in other complex diseases. In this review, we introduce guidelines on how to utilize deep learning methodologies and tools for drug repurposing. We first summarized the commonly used bioinformatics and pharmacogenomics databases for drug repurposing. Next, we discuss recently developed sequence-based and graph-based representation approaches as well as state-of-the-art deep learning-based methods. Finally, we present applications of drug repurposing to fight the COVID-19 pandemic, and outline its future challenges.

Structure-Preserving Graph Kernel for Brain Network Classification

This paper presents a novel graph-based kernel learning approach for connectome analysis. Specifically, we demonstrate how to leverage the naturally available structure within the graph representation to encode prior knowledge in the kernel. We first proposed a matrix factorization to directly extract structural features from natural symmetric graph representations of connectome data. We then used them to derive a structure-persevering graph kernel to be fed into the support vector machine. The proposed approach has the advantage of being clinically interpretable. Quantitative evaluations on challenging HIV disease classification (DTI- and fMRI-derived connectome data) and emotion recognition (EEG-derived connectome data) tasks demonstrate the superior performance of our proposed methods against the state-of-the-art. Results showed that relevant EEG-connectome information is primarily encoded in the alpha band during the emotion regulation task.

HETFORMER: Heterogeneous Transformer with Sparse Attention for Long-Text Extractive Summarization

To capture the semantic graph structure from raw text, most existing summarization approaches are built on GNNs with a pre-trained model. However, these methods suffer from cumbersome procedures and inefficient computations for long-text documents. To mitigate these issues, this paper proposes HETFORMER, a Transformer-based pre-trained model with multi-granularity sparse attentions for long-text extractive summarization. Specifically, we model different types of semantic nodes in raw text as a potential heterogeneous graph and directly learn heterogeneous relationships (edges) among nodes by Transformer. Extensive experiments on both single- and multi-document summarization tasks show that HETFORMER achieves state-of-the-art performance in Rouge F1 while using less memory and fewer parameters.

Multiplex Graph Networks for Multimodal Brain Network Analysis

In this paper, we propose MGNet, a simple and effective multiplex graph convolutional network (GCN) model for multimodal brain network analysis. The proposed method integrates tensor representation into the multiplex GCN model to extract the latent structures of a set of multimodal brain networks, which allows an intuitive 'grasping' of the common space for multimodal data. Multimodal representations are then generated with multiplex GCNs to capture specific graph structures. We conduct classification task on two challenging real-world datasets (HIV and Bipolar disorder), and the proposed MGNet demonstrates state-of-the-art performance compared to competitive benchmark methods. Apart from objective evaluations, this study may bear special significance upon network theory to the understanding of human connectome in different modalities. The code is available at https://github.com/ZhaomingKong/MGNets.

BrainNNExplainer: An Interpretable Graph Neural Network Framework for Brain Network based Disease Analysis

Interpretable brain network models for disease prediction are of great value for the advancement of neuroscience. GNNs are promising to model complicated network data, but they are prone to overfitting and suffer from poor interpretability, which prevents their usage in decision-critical scenarios like healthcare. To bridge this gap, we propose BrainNNExplainer, an interpretable GNN framework for brain network analysis. It is mainly composed of two jointly learned modules: a backbone prediction model that is specifically designed for brain networks and an explanation generator that highlights disease-specific prominent brain network connections. Extensive experimental results with visualizations on two challenging disease prediction datasets demonstrate the unique interpretability and outstanding performance of BrainNNExplainer.

Multi-VAE: Learning Disentangled View-common and View-peculiar Visual Representations for Multi-view Clustering

Multi-view clustering, a long-standing and important research problem, focuses on mining complementary information from diverse views. However, existing works often fuse multiple views' representations or handle clustering in a common feature space, which may result in their entanglement especially for visual representations. To address this issue, we present a novel VAE-based multi-view clustering framework (Multi-VAE) by learning disentangled visual representations. Concretely, we define a view-common variable and multiple view-peculiar variables in the generative model. The prior of view-common variable obeys approximately discrete Gumbel Softmax distribution, which is introduced to extract the common cluster factor of multiple views. Meanwhile, the prior of view-peculiar variable follows continuous Gaussian distribution, which is used to represent each view's peculiar visual factors. By controlling the mutual information capacity to disentangle the view-common and view-peculiar representations, continuous visual information of multiple views can be separated so that their common discrete cluster information can be effectively mined. Experimental results demonstrate that Multi-VAE enjoys the disentangled and explainable visual representations, while obtaining superior clustering performance compared with state-of-the-art methods.

Joint Embedding of Structural and Functional Brain Networks with Graph Neural Networks for Mental Illness Diagnosis

Multimodal brain networks characterize complex connectivities among different brain regions from both structural and functional aspects and provide a new means for mental disease analysis. Recently, Graph Neural Networks (GNNs) have become a de facto model for analyzing graph-structured data. However, how to employ GNNs to extract effective representations from brain networks in multiple modalities remains rarely explored. Moreover, as brain networks provide no initial node features, how to design informative node attributes and leverage edge weights for GNNs to learn is left unsolved. To this end, we develop a novel multiview GNN for multimodal brain networks. In particular, we regard each modality as a view for brain networks and employ contrastive learning for multimodal fusion. Then, we propose a GNN model which takes advantage of the message passing scheme by propagating messages based on degree statistics and brain region connectivities. Extensive experiments on two real-world disease datasets (HIV and Bipolar) demonstrate the effectiveness of our proposed method over state-of-the-art baselines.

Contrastive Multi-Modal Clustering

Multi-modal clustering, which explores complementary information from multiple modalities or views, has attracted people's increasing attentions. However, existing works rarely focus on extracting high-level semantic information of multiple modalities for clustering. In this paper, we propose Contrastive Multi-Modal Clustering (CMMC) which can mine high-level semantic information via contrastive learning. Concretely, our framework consists of three parts. (1) Multiple autoencoders are optimized to maintain each modality's diversity to learn complementary information. (2) A feature contrastive module is proposed to learn common high-level semantic features from different modalities. (3) A label contrastive module aims to learn consistent cluster assignments for all modalities. By the proposed multi-modal contrastive learning, the mutual information of high-level features is maximized, while the diversity of the low-level latent features is maintained. In addition, to utilize the learned high-level semantic features, we further generate pseudo labels by solving a maximum matching problem to fine-tune the cluster assignments. Extensive experiments demonstrate that CMMC has good scalability and outperforms state-of-the-art multi-modal clustering methods.