Temporal knowledge graph (TKG) reasoning is potent for discovering plausible facts with observable knowledge. However, evolving TKGs often bring newly unseen entities, relations, and timestamps, which pose significant challenges for current TKG reasoning methods as they struggle to extrapolate facts involving unseen components. We term this realistic yet under-investigated problem as full extrapolation over TKGs, aiming to model all unseen components for reasoning within evolving TKGs. To tackle this, we propose a novel contrastive variational graph symmetric autoencoder (CVGSAE) framework under the meta-learning setting. Initially, we first extract the spatiotemporal connections between relations and integrate a functional time encoding strategy to simultaneously initialize unseen entities, relations, and timestamps. Subsequently, we design an interactive variational graph symmetric autoencoder to encode and then reconstruct entity and relation representations by capturing their interactions to generate contrastive views. Finally, a dual-contrastive learning scheme is imposed on the encoded and reconstructed representations of both entities and relations to enhance their discriminability and task relevance. Extensive experiments on two benchmark datasets demonstrate that CVGSAE yields significant advancements beyond state-of-the-art baselines across all evaluation metrics. The source code is available at:https://github.com/hcfun/CVGSAE

Multi-modal knowledge graph reasoning (MKGR) seeks to conjecture plausible facts in MKGs by learning effective representations from various modalities (e.g., structure, text, and image). However, due to holistic redundancy (i.e., each modality carries task-irrelevant redundancy) and modality conflict (i.e., different modalities contain contradictory information), the reasoning performance of current methods is substantially impaired. In this paper, we propose a novel Consistency Discovery-guided Information Bottleneck (CDIB) framework to address the aforementioned challenges. Specifically, a modality compression module is first designed to learn modality-private entity representations of alleviating redundant information. Then, a consistency discovery module is developed to discover cross-modal consistency during multi-modal fusion to learn the comprehensive entity representations. To retain task-relevant information, an information preservation module is devised to further enrich the comprehensive entity representations to be predictive for MKGR. Extensive experiments indicate that CDIB achieves state-of-the-art reasoning ability on two benchmark datasets over current MKGR baselines, and also exhibits promising robustness against noise.

MOTIVATION: Predicting the associations between human microbes and drugs (MDAs) is one critical step in drug development and precision medicine areas. Since discovering these associations through wet experiments is time-consuming and labor-intensive, computational methods have already been an effective way to tackle this problem. Recently, graph contrastive learning (GCL) approaches have shown great advantages in learning the embeddings of nodes from heterogeneous biological graphs (HBGs). However, most GCL-based approaches don't fully capture the rich structure information in HBGs. Besides, fewer MDA prediction methods could screen out the most informative negative samples for effectively training the classifier. Therefore, it still needs to improve the accuracy of MDA predictions. RESULTS: In this study, we propose a novel approach that employs the Structure-enhanced Contrastive learning and Self-paced negative sampling strategy for Microbe-Drug Association predictions (SCSMDA). Firstly, SCSMDA constructs the similarity networks of microbes and drugs, as well as their different meta-path-induced networks. Then SCSMDA employs the representations of microbes and drugs learned from meta-path-induced networks to enhance their embeddings learned from the similarity networks by the contrastive learning strategy. After that, we adopt the self-paced negative sampling strategy to select the most informative negative samples to train the MLP classifier. Lastly, SCSMDA predicts the potential microbe-drug associations with the trained MLP classifier. The embeddings of microbes and drugs learning from the similarity networks are enhanced with the contrastive learning strategy, which could obtain their discriminative representations. Extensive results on three public datasets indicate that SCSMDA significantly outperforms other baseline methods on the MDA prediction task. Case studies for two common drugs could further demonstrate the effectiveness of SCSMDA in finding novel MDA associations. AVAILABILITY: The source code is publicly available on GitHub https://github.com/Yue-Yuu/SCSMDA-master.

The measurement of gene functional similarity plays a critical role in numerous biological applications, such as gene clustering, the construction of gene similarity networks. However, most existing approaches still rely heavily on traditional computational strategies, which are not guaranteed to achieve satisfactory performance. In this study, we propose a novel computational approach called GOGCN to measure gene functional similarity by modeling the Gene Ontology (GO) through Graph Convolutional Network (GCN). GOGCN is a graph-based approach that performs sufficient representation learning for terms and relations in the GO graph. First, GOGCN employs the GCN-based knowledge graph embedding (KGE) model to learn vector representations (i.e., embeddings) for all entities (i.e., terms). Second, GOGCN calculates the semantic similarity between two terms based on their corresponding vector representations. Finally, GOGCN estimates gene functional similarity by making use of the pair-wise strategy. During the representation learning period, GOGCN promotes semantic interaction between terms through GCN, thereby capturing the rich structural information of the GO graph. Further experimental results on various datasets suggest that GOGCN is superior to the other state-of-the-art approaches, which shows its reliability and effectiveness.

MOTIVATION: Discovering the drug-target interactions (DTIs) is a crucial step in drug development such as the identification of drug side effects and drug repositioning. Since identifying DTIs by web-biological experiments is time-consuming and costly, many computational-based approaches have been proposed and have become an efficient manner to infer the potential interactions. Although extensive effort is invested to solve this task, the prediction accuracy still needs to be improved. More especially, heterogeneous network-based approaches do not fully consider the complex structure and rich semantic information in these heterogeneous networks. Therefore, it is still a challenge to predict DTIs efficiently. RESULTS: In this study, we develop a novel method via Multiview heterogeneous information network embedding with Hierarchical Attention mechanisms to discover potential Drug-Target Interactions (MHADTI). Firstly, MHADTI constructs different similarity networks for drugs and targets by utilizing their multisource information. Combined with the known DTI network, three drug-target heterogeneous information networks (HINs) with different views are established. Secondly, MHADTI learns embeddings of drugs and targets from multiview HINs with hierarchical attention mechanisms, which include the node-level, semantic-level and graph-level attentions. Lastly, MHADTI employs the multilayer perceptron to predict DTIs with the learned deep feature representations. The hierarchical attention mechanisms could fully consider the importance of nodes, meta-paths and graphs in learning the feature representations of drugs and targets, which makes their embeddings more comprehensively. Extensive experimental results demonstrate that MHADTI performs better than other SOTA prediction models. Moreover, analysis of prediction results for some interested drugs and targets further indicates that MHADTI has advantages in discovering DTIs. AVAILABILITY AND IMPLEMENTATION: https://github.com/pxystudy/MHADTI.

BACKGROUND: Recently, with the foundation and development of gene ontology (GO) resources, numerous works have been proposed to compute functional similarity of genes and achieved series of successes in some research fields. Focusing on the calculation of the information content (IC) of terms is the main idea of these methods, which is essential for measuring functional similarity of genes. However, most approaches have some deficiencies, especially when measuring the IC of both GO terms and their corresponding annotated term sets. To this end, measuring functional similarity of genes accurately is still challenging. RESULTS: In this article, we proposed a novel gene functional similarity calculation method, which especially encapsulates the specificity of terms and edges (STE). The proposed method mainly contains three steps. Firstly, a novel computing model is put forward to compute the IC of terms. This model has the ability to exploit the specific structural information of GO terms. Secondly, the IC of term sets are computed by capturing the genetic structure between the terms contained in the set. Lastly, we measure the gene functional similarity according to the IC overlap ratio of the corresponding annotated genes sets. The proposed method accurately measures the IC of not only GO terms but also the annotated term sets by leveraging the specificity of edges in the GO graph. CONCLUSIONS: We conduct experiments on gene functional classification in biological pathways, gene expression datasets, and protein-protein interaction datasets. Extensive experimental results show the better performances of our proposed STE against several baseline methods.

In recent years, functional similarity has played an independent role in some biological fields such as gene clustering, gene functional prediction, and evaluation for protein-protein interaction. In this premise, some effective methods have already been proposed based on Gene Ontology (GO). Although these mainstream methods achieve the purpose for measuring gene functional similarity, they may have some deficiency when calculating the Information Content (IC) of GO terms. Consequently, measuring the functional similarity accurately is still a meaningful objective of research. In this paper, a novel method called SWE, is proposed for measuring gene functional similarity based on the GO graph. Firstly, an algorithm to measure terms' semantics based on their information in the GO graph is put forward. The information of GO terms mainly contains their depth, ancestors and descendants. Secondly, we calculate the IC of a term set by means of retrieving the inherited relationship between terms in a term set. Finally, the functional similarity between two genes is computed based on the IC overlap ratio of term sets annotating two genes respectively. Results demonstrate that SWE is superior to existing methods in some experiments such as functional classification of genes in a biological pathway, protein-protein interaction and gene expression experiment. Further analysis demonstrates that SWE takes not only the specificity of terms into account, but their information in the GO graph, both of which are shown to be consistent with human perspectives.