MUSCLE: multi-view and multi-scale attentional feature fusion for microRNA-disease associations prediction.

MicroRNAs (miRNAs) synergize with various biomolecules in human cells resulting in diverse functions in regulating a wide range of biological processes. Predicting potential disease-associated miRNAs as valuable biomarkers contributes to the treatment of human diseases. However, few previous methods take a holistic perspective and only concentrate on isolated miRNA and disease objects, thereby ignoring that human cells are responsible for multiple relationships. In this work, we first constructed a multi-view graph based on the relationships between miRNAs and various biomolecules, and then utilized graph attention neural network to learn the graph topology features of miRNAs and diseases for each view. Next, we added an attention mechanism again, and developed a multi-scale feature fusion module, aiming to determine the optimal fusion results for the multi-view topology features of miRNAs and diseases. In addition, the prior attribute knowledge of miRNAs and diseases was simultaneously added to achieve better prediction results and solve the cold start problem. Finally, the learned miRNA and disease representations were then concatenated and fed into a multi-layer perceptron for end-to-end training and predicting potential miRNA-disease associations. To assess the efficacy of our model (called MUSCLE), we performed 5- and 10-fold cross-validation (CV), which got average the Area under ROC curves of 0.966${\pm }$0.0102 and 0.973${\pm }$0.0135, respectively, outperforming most current state-of-the-art models. We then examined the impact of crucial parameters on prediction performance and performed ablation experiments on the feature combination and model architecture. Furthermore, the case studies about colon cancer, lung cancer and breast cancer also fully demonstrate the good inductive capability of MUSCLE. Our data and code are free available at a public GitHub repository: https://github.com/zht-code/MUSCLE.git.

A multi-source molecular network representation model for protein-protein interactions prediction.

The prediction of potential protein-protein interactions (PPIs) is a critical step in decoding diseases and understanding cellular mechanisms. Traditional biological experiments have identified plenty of potential PPIs in recent years, but this problem is still far from being solved. Hence, there is urgent to develop computational models with good performance and high efficiency to predict potential PPIs. In this study, we propose a multi-source molecular network representation learning model (called MultiPPIs) to predict potential protein-protein interactions. Specifically, we first extract the protein sequence features according to the physicochemical properties of amino acids by utilizing the auto covariance method. Second, a multi-source association network is constructed by integrating the known associations among miRNAs, proteins, lncRNAs, drugs, and diseases. The graph representation learning method, DeepWalk, is adopted to extract the multisource association information of proteins with other biomolecules. In this way, the known protein-protein interaction pairs can be represented as a concatenation of the protein sequence and the multi-source association features of proteins. Finally, the Random Forest classifier and corresponding optimal parameters are used for training and prediction. In the results, MultiPPIs obtains an average 86.03% prediction accuracy with 82.69% sensitivity at the AUC of 93.03% under five-fold cross-validation. The experimental results indicate that MultiPPIs has a good prediction performance and provides valuable insights into the field of potential protein-protein interactions prediction. MultiPPIs is free available at https://github.com/jiboyalab/multiPPIs .

MHGTMDA: Molecular heterogeneous graph transformer based on biological entity graph for miRNA-disease associations prediction.

MicroRNAs (miRNAs) play a crucial role in the prevention, prognosis, diagnosis, and treatment of complex diseases. Existing computational methods primarily focus on biologically relevant molecules directly associated with miRNA or disease, overlooking the fact that the human body is a highly complex system where miRNA or disease may indirectly correlate with various types of biomolecules. To address this, we propose a novel prediction model named MHGTMDA (miRNA and disease association prediction using heterogeneous graph transformer based on molecular heterogeneous graph). MHGTMDA integrates biological entity relationships of eight biomolecules, constructing a relatively comprehensive heterogeneous biological entity graph. MHGTMDA serves as a powerful molecular heterogeneity map transformer, capturing structural elements and properties of miRNAs and diseases, revealing potential associations. In a 5-fold cross-validation study, MHGTMDA achieved an area under the receiver operating characteristic curve of 0.9569, surpassing state-of-the-art methods by at least 3%. Feature ablation experiments suggest that considering features among multiple biomolecules is more effective in uncovering miRNA-disease correlations. Furthermore, we conducted differential expression analyses on breast cancer and lung cancer, using MHGTMDA to further validate differentially expressed miRNAs. The results demonstrate MHGTMDA's capability to identify novel MDAs.

HyperVR: a hybrid deep ensemble learning approach for simultaneously predicting virulence factors and antibiotic resistance genes.

Infectious diseases emerge unprecedentedly, posing serious challenges to public health and the global economy. Virulence factors (VFs) enable pathogens to adhere, reproduce and cause damage to host cells, and antibiotic resistance genes (ARGs) allow pathogens to evade otherwise curable treatments. Simultaneous identification of VFs and ARGs can save pathogen surveillance time, especially in situ epidemic pathogen detection. However, most tools can only predict either VFs or ARGs. Few tools that predict VFs and ARGs simultaneously usually have high false-negative rates, are sensitive to the cutoff thresholds and can only identify conserved genes. For better simultaneous prediction of VFs and ARGs, we propose a hybrid deep ensemble learning approach called HyperVR. By considering both best hit scores and statistical gene sequence patterns, HyperVR combines classical machine learning and deep learning to simultaneously and accurately predict VFs, ARGs and negative genes (neither VFs nor ARGs). For the prediction of individual VFs and ARGs, in silico spike-in experiment (the VFs and ARGs in real metagenomic data), and pseudo-VFs and -ARGs (gene fragments), HyperVR outperforms the current state-of-the-art prediction tools. HyperVR uses only gene sequence information without strict cutoff thresholds, hence making prediction straightforward and reliable.

SPRDA: a link prediction approach based on the structural perturbation to infer disease-associated Piwi-interacting RNAs.

piRNA and PIWI proteins have been confirmed for disease diagnosis and treatment as novel biomarkers due to its abnormal expression in various cancers. However, the current research is not strong enough to further clarify the functions of piRNA in cancer and its underlying mechanism. Therefore, how to provide large-scale and serious piRNA candidates for biological research has grown up to be a pressing issue. In this study, a novel computational model based on the structural perturbation method is proposed to predict potential disease-associated piRNAs, called SPRDA. Notably, SPRDA belongs to positive-unlabeled learning, which is unaffected by negative examples in contrast to previous approaches. In the 5-fold cross-validation, SPRDA shows high performance on the benchmark dataset piRDisease, with an AUC of 0.9529. Furthermore, the predictive performance of SPRDA for 10 diseases shows the robustness of the proposed method. Overall, the proposed approach can provide unique insights into the pathogenesis of the disease and will advance the field of oncology diagnosis and treatment.

SMMDA: Predicting miRNA-Disease Associations by Incorporating Multiple Similarity Profiles and a Novel Disease Representation.

Increasing evidence has suggested that microRNAs (miRNAs) are significant in research on human diseases. Predicting possible associations between miRNAs and diseases would provide new perspectives on disease diagnosis, pathogenesis, and gene therapy. However, considering the intrinsic time-consuming and expensive cost of traditional Vitro studies, there is an urgent need for a computational approach that would allow researchers to identify potential associations between miRNAs and diseases for further research. In this paper, we presented a novel computational method called SMMDA to predict potential miRNA-disease associations. In particular, SMMDA first utilized a new disease representation method (MeSHHeading2vec) based on the network embedding algorithm and then fused it with Gaussian interaction profile kernel similarity information of miRNAs and diseases, disease semantic similarity, and miRNA functional similarity. Secondly, SMMDA utilized a deep auto-coder network to transform the original features further to achieve a better feature representation. Finally, the ensemble learning model, XGBoost, was used as the underlying training and prediction method for SMMDA. In the results, SMMDA acquired a mean accuracy of 86.68% with a standard deviation of 0.42% and a mean AUC of 94.07% with a standard deviation of 0.23%, outperforming many previous works. Moreover, we also compared the predictive ability of SMMDA with different classifiers and different feature descriptors. In the case studies of three common Human diseases, the top 50 candidate miRNAs have 47 (esophageal neoplasms), 48 (breast neoplasms), and 48 (colon neoplasms) are successfully verified by two other databases. The experimental results proved that SMMDA has a reliable prediction ability in predicting potential miRNA-disease associations. Therefore, it is anticipated that SMMDA could be an effective tool for biomedical researchers.

MFDNN: multi-channel feature deep neural network algorithm to identify COVID19 chest X-ray images.

The use of chest X-ray images (CXI) to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) caused by Coronavirus Disease 2019 (COVID19) is life-saving important for both patients and doctors. This research proposes a multi-channel feature deep neural network (MFDNN) algorithm to screen people infected with COVID19. The algorithm integrates data over-sampling technology and MFDNN model to carry out the training. The oversampling technique reduces the deviation of the prior probability of the MFDNN algorithm on unbalanced data. Multi-channel feature fusion technology improves the efficiency of feature extraction and the accuracy of model diagnosis. In the experiment, Compared with traditional deep learning models (VGG19, GoogLeNet, Resnet50, Desnet201), the MFDNN model obtains an average test accuracy of 93.19% in all data. Furthermore, in each type of screening, the precision, recall, and F1 Score of the MFDNN model are also better than traditional deep learning networks. Furthermore, through ablation experiments, we proved that a multi-channel convolutional neural network (CNN) is superior to single-channel CNN, additional layer and PSN module, and indirectly proved the sufficiency and necessity of each step of the MFDNN classification method. Finally, our experimental code will be placed at https://github.com/panliangrui/covid19.

SANE: A sequence combined attentive network embedding model for COVID-19 drug repositioning.

The COVID-19 has now spread all over the world and causes a huge burden for public health and world economy. Drug repositioning has become a promising treatment strategy in COVID-19 crisis because it can shorten drug development process, reduce pharmaceutical costs and reposition approval drugs. Existing computational methods only focus on single information, such as drug and virus similarity or drug-virus network feature, which is not sufficient to predict potential drugs. In this paper, a sequence combined attentive network embedding model SANE is proposed for identifying drugs based on sequence features and network features. On the one hand, drug SMILES and virus sequence features are extracted by encoder-decoder in SANE as node initial embedding in drug-virus network. On the other hand, SANE obtains fields for each node by attention-based Depth-First-Search (DFS) to reduce noises and improve efficiency in representation learning and adopts a bottom-up aggregation strategy to learn node network representation from selected fields. Finally, a forward neural network is used for classifying. Experiment results show that SANE has achieved the performance with 81.98% accuracy and 0.8961 AUC value and outperformed state-of-the-art baselines. Further case study on COVID-19 indicates that SANE has a strong predictive ability since 25 of the top 40 (62.5%) drugs are verified by valuable dataset and literatures. Therefore, SANE is powerful to reposition drugs for COVID-19 and provides a new perspective for drug repositioning.

DANE-MDA: Predicting microRNA-disease associations via deep attributed network embedding.

Predicting the microRNA-disease associations by using computational methods is conductive to the efficiency of costly and laborious traditional bio-experiments. In this study, we propose a computational machine learning-based method (DANE-MDA) that preserves integrated structure and attribute features via deep attributed network embedding to predict potential miRNA-disease associations. Specifically, the integrated features are extracted by using deep stacked auto-encoder on the diverse orders of matrixes containing structure and attribute information and are then trained by using random forest classifier. Under 5-fold cross-validation experiments, DANE-MDA yielded average accuracy, sensitivity, and AUC at 85.59%, 84.23%, and 0.9264 in term of HMDD v3.0 dataset, and 83.21%, 80.39%, and 0.9113 in term of HMDD v2.0 dataset, respectively. Additionally, case studies on breast, colon, and lung neoplasms related disease show that 47, 47, and 46 of the top 50 miRNAs can be predicted and retrieved in the other database.

Prediction of lncRNA-disease associations via an embedding learning HOPE in heterogeneous information networks.

Uncovering additional long non-coding RNA (lncRNA)-disease associations has become increasingly important for developing treatments for complex human diseases. Identification of lncRNA biomarkers and lncRNA-disease associations is central to diagnoses and treatment. However, traditional experimental methods are expensive and time-consuming. Enormous amounts of data present in public biological databases are available for computational methods used to predict lncRNA-disease associations. In this study, we propose a novel computational method to predict lncRNA-disease associations. More specifically, a heterogeneous network is first constructed by integrating the associations among microRNA (miRNA), lncRNA, protein, drug, and disease, Second, high-order proximity preserved embedding (HOPE) was used to embed nodes into a network. Finally, the rotation forest classifier was adopted to train the prediction model. In the 5-fold cross-validation experiment, the area under the curve (AUC) of our method achieved 0.8328 ± 0.0236. We compare it with the other four classifiers, in which the proposed method remarkably outperformed other comparison methods. Otherwise, we constructed three case studies for three excess death rate cancers, respectively. The results show that 9 (lung cancer, gastric cancer, and hepatocellular carcinomas) out of the top 15 predicted disease-related lncRNAs were confirmed by our method. In conclusion, our method could predict the unknown lncRNA-disease associations effectively.

NEMPD: a network embedding-based method for predicting miRNA-disease associations by preserving behavior and attribute information.

BACKGROUND: As an important non-coding RNA, microRNA (miRNA) plays a significant role in a series of life processes and is closely associated with a variety of Human diseases. Hence, identification of potential miRNA-disease associations can make great contributions to the research and treatment of Human diseases. However, to our knowledge, many existing computational methods only utilize the single type of known association information between miRNAs and diseases to predict their potential associations, without focusing on their interactions or associations with other types of molecules. RESULTS: In this paper, we propose a network embedding-based method for predicting miRNA-disease associations by preserving behavior and attribute information. Firstly, a heterogeneous network is constructed by integrating known associations among miRNA, protein and disease, and the network representation method Learning Graph Representations with Global Structural Information (GraRep) is implemented to learn the behavior information of miRNAs and diseases in the network. Then, the behavior information of miRNAs and diseases is combined with the attribute information of them to represent miRNA-disease association pairs. Finally, the prediction model is established based on the Random Forest algorithm. Under the five-fold cross validation, the proposed NEMPD model obtained average 85.41% prediction accuracy with 80.96% sensitivity at the AUC of 91.58%. Furthermore, the performance of NEMPD is also validated by the case studies. Among the top 50 predicted disease-related miRNAs, 48 (breast neoplasms), 47 (colon neoplasms), 47 (lung neoplasms) were confirmed by two other databases. CONCLUSIONS: The proposed NEMPD model has a good performance in predicting the potential associations between miRNAs and diseases, and has great potency in the field of miRNA-disease association prediction in the future.

Prediction of drug-target interactions from multi-molecular network based on LINE network representation method.

BACKGROUND: The prediction of potential drug-target interactions (DTIs) not only provides a better comprehension of biological processes but also is critical for identifying new drugs. However, due to the disadvantages of expensive and high time-consuming traditional experiments, only a small section of interactions between drugs and targets in the database were verified experimentally. Therefore, it is meaningful and important to develop new computational methods with good performance for DTIs prediction. At present, many existing computational methods only utilize the single type of interactions between drugs and proteins without paying attention to the associations and influences with other types of molecules. METHODS: In this work, we developed a novel network embedding-based heterogeneous information integration model to predict potential drug-target interactions. Firstly, a heterogeneous multi-molecuar information network is built by combining the known associations among protein, drug, lncRNA, disease, and miRNA. Secondly, the Large-scale Information Network Embedding (LINE) model is used to learn behavior information (associations with other nodes) of drugs and proteins in the network. Hence, the known drug-protein interaction pairs can be represented as a combination of attribute information (e.g. protein sequences information and drug molecular fingerprints) and behavior information of themselves. Thirdly, the Random Forest classifier is used for training and prediction. RESULTS: In the results, under the five-fold cross validation, our method obtained 85.83% prediction accuracy with 80.47% sensitivity at the AUC of 92.33%. Moreover, in the case studies of three common drugs, the top 10 candidate targets have 8 (Caffeine), 7 (Clozapine) and 6 (Pioglitazone) are respectively verified to be associated with corresponding drugs. CONCLUSIONS: In short, these results indicate that our method can be a powerful tool for predicting potential drug-target interactions and finding unknown targets for certain drugs or unknown drugs for certain targets.

Predicting miRNA-disease association from heterogeneous information network with GraRep embedding model.

In recent years, accumulating evidences have shown that microRNA (miRNA) plays an important role in the exploration and treatment of diseases, so detection of the associations between miRNA and disease has been drawn more and more attentions. However, traditional experimental methods have the limitations of high cost and time- consuming, a computational method can help us more systematically and effectively predict the potential miRNA-disease associations. In this work, we proposed a novel network embedding-based heterogeneous information integration method to predict miRNA-disease associations. More specifically, a heterogeneous information network is constructed by combining the known associations among lncRNA, drug, protein, disease, and miRNA. After that, the network embedding method Learning Graph Representations with Global Structural Information (GraRep) is employed to learn embeddings of nodes in heterogeneous information network. In this way, the embedding representations of miRNA and disease are integrated with the attribute information of miRNA and disease (e.g. miRNA sequence information and disease semantic similarity) to represent miRNA-disease association pairs. Finally, the Random Forest (RF) classifier is used for predicting potential miRNA-disease associations. Under the 5-fold cross validation, our method obtained 85.11% prediction accuracy with 80.41% sensitivity at the AUC of 91.25%. In addition, in case studies of three major Human diseases, 45 (Colon Neoplasms), 42 (Breast Neoplasms) and 44 (Esophageal Neoplasms) of top-50 predicted miRNAs are respectively verified by other miRNA-disease association databases. In conclusion, the experimental results suggest that our method can be a powerful and useful tool for predicting potential miRNA-disease associations.