Taking incompatible multiple drugs together may cause adverse interactions and side effects on the body. Accurate prediction of drug-drug interaction (DDI) events is essential for avoiding this issue. Recently, various artificial intelligence-based approaches have been proposed for predicting DDI events. However, DDI events are associated with complex relationships and mechanisms among drugs, targets, enzymes, transporters, molecular structures, etc. Existing approaches either partially or loosely consider these relationships and mechanisms by a non-end-to-end learning framework, resulting in sub-optimal feature extractions and fusions for prediction. Different from them, this paper proposes a Multimodal Knowledge Graph Fused End-to-end Neural Network (MKGFENN) that consists of two main parts: multimodal knowledge graph (MKG) and fused end-to-end neural network (FENN). First, MKG is constructed by comprehensively exploiting DDI events-associated relationships and mechanisms from four knowledge graphs of drugs-chemical entities, drug-substructures, drugs-drugs, and molecular structures. Correspondingly, a four channels graph neural network is designed to extract high-order and semantic features from MKG. Second, FENN designs a multi-layer perceptron to fuse the extracted features by end-to-end learning. With such designs, the feature extractions and fusions of DDI events are guaranteed to be comprehensive and optimal for prediction. Through extensive experiments on real drug datasets, we demonstrate that MKG-FENN exhibits high accuracy and significantly outperforms state-of-the-art models in predicting DDI events. The source code and supplementary file of this article are available on: https://github.com/wudi1989/MKG-FENN.

Protein-protein interactions (PPIs) are essential to understanding cellular mechanisms, signaling networks, disease processes, and drug development, as they represent the physical contacts and functional associations between proteins. Recent advances have witnessed the achievements of artificial intelligence (AI) methods aimed at predicting PPIs. However, these approaches often handle the intricate web of relationships and mechanisms among proteins, drugs, diseases, ribonucleic acid (RNA), and protein structures in a fragmented or superficial manner. This is typically due to the limitations of non-end-to-end learning frameworks, which can lead to sub-optimal feature extraction and fusion, thereby compromising the prediction accuracy. To address these deficiencies, this paper introduces a novel end-to-end learning model, the Knowledge Graph Fused Graph Neural Network (KGF-GNN). This model comprises three integral components: (1) Protein Associated Network (PAN) Construction : We begin by constructing a PAN that extensively captures the diverse relationships and mechanisms linking proteins with drugs, diseases, RNA, and protein structures. (2) Graph Neural Network for Feature Extraction : A Graph Neural Network (GNN) is then employed to distill both topological and semantic features from the PAN, alongside another GNN designed to extract topological features directly from observed PPI networks. (3) Multi-layer Perceptron for Feature Fusion : Finally, a multi-layer perceptron integrates these varied features through end-to-end learning, ensuring that the feature extraction and fusion processes are both comprehensive and optimized for PPI prediction. Extensive experiments conducted on real-world PPI datasets validate the effectiveness of our proposed KGF-GNN approach, which not only achieves high accuracy in predicting PPIs but also significantly surpasses existing state-of-the-art models. This work not only enhances our ability to predict PPIs with a higher precision but also contributes to the broader application of AI in Bioinformatics, offering profound implications for biological research and therapeutic development.

Online learning with feature spaces that are not fixed but can vary over time renders a seemingly flexible learning paradigm thus has drawn much attention. Unfortunately, two restrictions prohibit a ubiquitous application of this learning paradigm in practice. First, whereas prior studies mainly assume a homogenous feature type, data streams generated from real applications can be heterogeneous in which Boolean, ordinal, and continuous co-exist. Existing methods that prescribe parametric distributions such as Gaussians would not suffice to model the correlation among such mixtyped features. Second, while full supervision seems to be a default setup, providing labels to all arriving data instances over a long time span is tangibly onerous, laborious, and economically unsustainable. Alas, a semi-supervised online learner that can deal with mix-typed, varying feature spaces is still missing. To fill the gap, this paper explores a novel problem, named Online Semi-supervised Learning with Mixtyped streaming Features (OSLMF), which strives to relax the restrictions on the feature type and supervision information. Our key idea to solve the new problem is to leverage copula model to align the data instances with different feature spaces so as to make their distance measurable. A geometric structure underlying data instances is then established in an online fashion based on their distances, through which the limited labeling information is propagated, from the scarce labeled instances to their close neighbors. Experimental results are documented to evidence the viability and effectiveness of our proposed approach. Code is released in https://github.com/wudi1989/OSLMF.

Although lycopene intake and risk of prostate cancer have been explored for decades, recent studies show that Non-Hispanic Black Prostate Cancer (PCa) patients benefit less than Non-Hispanic White patients from a lycopene intake intervention program. This study examined whether a lycopene intake-related racial disparity exists in reducing the risk of PCa in healthy adults. Data on healthy, cancer-free Non-Hispanic Black (NHB) men (n = 159) and Non-Hispanic White (NHW) men (n = 478) from the 2003 to 2010 NHANES dataset were analyzed. Total lycopene intake from daily diet, age, living status, race/ethnicity, education level, poverty income ratio, body mass index, and smoking status were studied as independent variables. The combination of total Prostate-Specific Antigen (PSA) level and the ratio of free PSA was set as criteria for evaluating the risk of PCa. Multivariable logistic regression was used in race-stratified analyses to compute odds ratios (OR) and 95% confidence intervals (95% CI) comparing high PCa risk with low PCa risk. We found, in the whole population, race/ethnicity was the only factor that influenced lycopene intake from the daily diet. NHB men consumed less lycopene than NHW men (3,716 vs. 6,487 (mcg), p = 0.01). Sufficient lycopene intake could reduce the risk of PCa (OR: 0.40, 95% CI: 0.18–0.85, p = 0.02). Men aged between 66 and 70 had high PCa risk (OR: 3.32, 95% CI: 1.12–9.85, p = 0.03). Obesity served as a protective factor against the high risk of PCa (OR: 0.25, 95% CI: 0.12–0.54, p = 0.001). NHW men aged between 66 and 70 had a high risk of PCa (OR: 4.01, 95% CI: 1.02–15.73, p = 0.05). Obese NHW men also had lower risk of PCa (OR: 0.18, 95% CI: 0.07–0.47 p = 0.001). NHB men had a high risk of PCa compared to NHW men (OR: 2.27, 95% CI: 1.35–3.81 p = 0.004). NHB men who were living without partners experienced an even higher risk of PCa (OR: 3.35, 95% CI: 1.01–11.19 p = 0.07). Sufficient lycopene intake from daily food could serve as a protector against PCa. Such an association was only observed in NHW men. Further studies are needed to explore the dose-response relationship between lycopene intake and the association of PCa risk in NHB men.

Multiobjective evacuation routes optimization problem is defined to find out optimal evacuation routes for a group of evacuees under multiple evacuation objectives. For improving the evacuation efficiency, we abstracted the evacuation zone as a superposed potential field network (SPFN), and we presented SPFN-based ACO algorithm (SPFN-ACO) to solve this problem based on the proposed model. In Wuhan Sports Center case, we compared SPFN-ACO algorithm with HMERP-ACO algorithm and traditional ACO algorithm under three evacuation objectives, namely, total evacuation time, total evacuation route length, and cumulative congestion degree. The experimental results show that SPFN-ACO algorithm has a better performance while comparing with HMERP-ACO algorithm and traditional ACO algorithm for solving multi-objective evacuation routes optimization problem.