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Abstract Circular RNA (CircRNA)–microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.

Circular RNA (CircRNA)–microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted. [ABSTRACT FROM AUTHOR]

Studying the association between microbes and diseases not only aids in the prevention and diagnosis of diseases, but also provides crucial theoretical support for new drug development and personalized treatment. Due to the time‐consuming and costly nature of laboratory‐based biological tests to confirm the relationship between microbes and diseases, there is an urgent need for innovative computational frameworks to anticipate new associations between microbes and diseases. Here, we propose a novel computational approach based on a dual branch graph convolutional network (GCN) module, abbreviated as DBGCNMDA, for identifying microbe–disease associations. First, DBGCNMDA calculates the similarity matrix of diseases and microbes by integrating functional similarity and Gaussian association spectrum kernel (GAPK) similarity. Then, semantic information from different biological networks is extracted by two GCN modules from different perspectives. Finally, the scores of microbe–disease associations are predicted based on the extracted features. The main innovation of this method lies in the use of two types of information for microbe/disease similarity assessment. Additionally, we extend the disease nodes to address the issue of insufficient features due to low data dimensionality. We optimize the connectivity between the homogeneous entities using random walk with restart (RWR), and then use the optimized similarity matrix as the initial feature matrix. In terms of network understanding, we design a dual branch GCN module, namely GlobalGCN and LocalGCN, to fine‐tune node representations by introducing side information, including homologous neighbour nodes. We evaluate the accuracy of the DBGCNMDA model using five‐fold cross‐validation (5‐fold‐CV) technique. The results show that the area under the receiver operating characteristic curve (AUC) and area under the precision versus recall curve (AUPR) of the DBGCNMDA model in the 5‐fold‐CV are 0.9559 and 0.9630, respectively. The results from the case studies using published experimental data confirm a significant number of predicted associations, indicating that DBGCNMDA is an effective tool for predicting potential microbe–disease associations. [ABSTRACT FROM AUTHOR]

Increasing research has shown that the abnormal expression of microRNA (miRNA) is associated with many complex diseases. However, biological experiments have many limitations in identifying the potential disease-miRNA associations. Therefore, we developed a computational model of Three-Layer Heterogeneous Network based on the Integration of CircRNA information for MiRNA-Disease Association prediction (TLHNICMDA). In the model, a disease-miRNA-circRNA heterogeneous network is built by known disease-miRNA associations, known miRNA-circRNA interactions, disease similarity, miRNA similarity, and circRNA similarity. Then, the potential disease-miRNA associations are identified by an update algorithm based on the global network. Finally, based on global and local leave-one-out cross validation (LOOCV), the values of AUCs in TLHNICMDA are 0.8795 and 0.7774. Moreover, the mean and standard deviation of AUC in 5-fold cross-validations is 0.8777 +/−0.0010. Especially, the two types of case studies illustrated the usefulness of TLHNICMDA in predicting disease-miRNA interactions. [ABSTRACT FROM AUTHOR]

Micro ribonucleic acids (miRNAs) can regulate the protein expression levels of genes in the human body and have recently been reported to be closely related to the cause of disease. Determining the genes related to miRNAs will aid in understanding the mechanisms underlying complex miRNAs. However, the identification of miRNA-related genes through wet experiments (in vivo, traditional methods are time- and cost-consuming). To overcome these problems, recent studies have investigated the prediction of miRNA relevance using deep learning models. This study presents a method for predicting the relationships between miRNAs and genes. First, we reconstruct a negative dataset using the proposed method. We then extracted the feature using an autoencoder, after which the feature vector was concatenated with the original data. Thereafter, the concatenated data were used to train a long short-term memory model. Our model exhibited an area under the curve of 0.9609, outperforming previously reported models trained using the same dataset. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small RNA molecules consisting of approximately 22 nucleotides; they regulate gene expression and are employed in the development of therapeutics for intractable diseases. Predicting the association between miRNAs and genes is crucial for understanding their roles in molecular processes. miRNA–gene associations have been studied using deep learning methods, but these methods present various constraints. Through addressing the limitations of previous methods, this study aimed to achieve better performance than the state-of-the-art (SOTA) methods for studying miRNA–gene associations. We constructed the most extensive embedded dataset to date, comprising 717,728 miRNA–gene pairs, specifically designed for our deep learning model. Further, we applied an embedding method used for protein embedding for transforming our gene sequence data. Moreover, we constructed a sophisticated negative dataset based on three distance criteria, unlike most studies that randomly designate negative data. Leveraging the data and insights from these approaches, we built a deep learning model with the best performance among SOTA miRNA–gene studies (area under the receiver operating characteristic curve = 0.9834). In addition, we conducted a case study using the learned model to predict potential positive data. We also aimed to identify miRNAs closely associated with a gene linked to various cancers. [ABSTRACT FROM AUTHOR]

Introduction: With the increasingly serious problem of antiviral drug resistance, drug repurposing offers a time-efficient and cost-effective way to find potential therapeutic agents for disease. Computational models have the ability to quickly predict potential reusable drug candidates to treat diseases. Methods: In this study, two matrix decomposition-based methods, i.e., Matrix Decomposition with Heterogeneous Graph Inference (MDHGI) and Bounded Nuclear Norm Regularization (BNNR), were integrated to predict anti-viral drugs. Moreover, global leave-one-out cross-validation (LOOCV), local LOOCV, and 5-fold cross-validation were implemented to evaluate the performance of the proposed model based on datasets of DrugVirus that consist of 933 known associations between 175 drugs and 95 viruses. Results: The results showed that the area under the receiver operating characteristics curve (AUG) of global LOOCV and local LOOCV are 0.9035 and 0.8786, respectively. The average AUC and the standard deviation of the 5-fold cross-validation for DrugVirus datasets are 0.8856 ± 0.0032. We further implemented cross-validation based on MDAD and aBiofilm, respectively, to evaluate the performance of the model. In particle, MDAD (aBiofilm) dataset contains 2,470 (2,884) known associations between 1,373 (1,470) drugs and 173 (140) microbes. In addition, two types of case studies were carried out further to verify the effectiveness of the model based on the DrugVirus and MDAD datasets. The results of the case studies supported the effectiveness of MHBVDA in identifying potential virus-drug associations as well as predicting potential drugs for new microbes. [ABSTRACT FROM AUTHOR]

Dysregulation of microRNAs (miRNAs) is closely associated with refractory human diseases, and the identification of potential associations between small molecule (SM) drugs and miRNAs can provide valuable insights for clinical treatment. Existing computational techniques for inferring potential associations suffer from limitations in terms of accuracy and efficiency. To address these challenges, we devise a novel predictive model called RPCA |$\Gamma $| NR, in which we propose a new Robust principal component analysis (PCA) framework based on |$\gamma $| -norm and |$l_{2,1}$| -norm regularization and design an Augmented Lagrange Multiplier method to optimize it, thereby deriving the association scores. The Gaussian Interaction Profile Kernel Similarity is calculated to capture the similarity information of SMs and miRNAs in known associations. Through extensive evaluation, including Cross Validation Experiments, Independent Validation Experiment, Efficiency Analysis, Ablation Experiment, Matrix Sparsity Analysis, and Case Studies, RPCA |$\Gamma $| NR outperforms state-of-the-art models concerning accuracy, efficiency and robustness. In conclusion, RPCA |$\Gamma $| NR can significantly streamline the process of determining SM–miRNA associations, thus contributing to advancements in drug development and disease treatment. [ABSTRACT FROM AUTHOR]

Clinical trials indicate that the dysregulation of microRNAs (miRNAs) is closely associated with the development of diseases. Therefore, predicting miRNA-disease associations is significant for studying the pathogenesis of diseases. Since traditional wet-lab methods are resource-intensive, cost-saving computational models can be an effective complementary tool in biological experiments. In this work, a locality-constrained linear coding is proposed to predict associations (ILLCEL). Among them, ILLCEL adopts miRNA sequence similarity, miRNA functional similarity, disease semantic similarity, and interaction profile similarity obtained by locality-constrained linear coding (LLC) as the priori information. Next, features and similarities extracted from multiperspectives are input to the ensemble learning framework to improve the comprehensiveness of the prediction. Significantly, the introduction of hypergraph-regular terms improves the accuracy of prediction by describing complex associations between samples. The results under fivefold cross validation indicate that ILLCEL achieves superior prediction performance. In case studies, known associations are accurately predicted and novel associations are verified in HMDD v3.2, miRCancer, and existing literature. It is concluded that ILLCEL can be served as a powerful tool for inferring potential associations. [ABSTRACT FROM AUTHOR]

Background. A growing number of experiments have shown that microRNAs (miR- NAs) can be used as target of small molecules (SMs) to regulate gene expression for treating diseases. Therefore, identifying SM-related miRNAs is helpful for the treatment of diseases in the domain of medical investigation. Methods. This article presents a new computational model, called NIRBMSMMA (neighborhood-based inference (NI) and restricted Boltzmann machine (RBM)), which we developed to identify potential small molecule-miRNA associations (NIRBMSMMA). First, grounded on known SM-miRNAs associations, SM similarity and miRNA similarity, NI was used to predict score of an unknown SM-miRNA pair by reckoning the sum of known associations between neighbors of the SM (miRNA) and the miRNA (SM). Second, utilizing a two-layered generative stochastic artificial neural network, RBM was used to predict SM-miRNA association by learning potential probability distribution from known SM-miRNA associations. At last, an ensemble learning model was conducted to combine NI and RBM for identifying potential SM- miRNA associations. Results. Furthermore, we conducted global leave one out cross validation (LOOCV), miRNA-fixed LOOCV, SM-fixed LOOCV and five-fold cross validation to as- sess performance of NIRBMSMMA based on three datasets. Results showed that NIRBMSMMA obtained areas under the curve (AUC) of 0.9912, 0.9875, 0.8376 and 0.9898 ± 0.0009 under global LOOCV, miRNA-fixed LOOCV, SM-fixed LOOCV and five-fold cross validation based on dataset 1, respectively. For dataset 2, the AUCs are 0.8645, 0.8720, 0.7066 and 0.8547 ± 0.0046 in turn. For dataset 3, the AUCs are 0.9884, 0.9802, 0.8239 and 0.9870 ± 0.0015 in turn. Also, we conducted case studies to further assess the predictive performance of NIRBMSMMA. These results illustrated the proposed model is a useful tool in predicting potential SM-miRNA associations. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have significant implications in diverse human diseases and have proven to be effectively targeted by small molecules (SMs) for therapeutic interventions. However, current SM–miRNA association prediction models do not adequately capture SM/miRNA similarity. Matrix completion is an effective method for association prediction, but existing models use nuclear norm instead of rank function, which has some drawbacks. Therefore, we proposed a new approach for predicting SM–miRNA associations by utilizing the truncated schatten p-norm (TSPN). First, the SM/miRNA similarity was preprocessed by incorporating the Gaussian interaction profile kernel similarity method. This identified more SM/miRNA similarities and significantly improved the SM–miRNA prediction accuracy. Next, we constructed a heterogeneous SM–miRNA network by combining biological information from three matrices and represented the network with its adjacency matrix. Finally, we constructed the prediction model by minimizing the truncated schatten p-norm of this adjacency matrix and we developed an efficient iterative algorithmic framework to solve the model. In this framework, we also used a weighted singular value shrinkage algorithm to avoid the problem of excessive singular value shrinkage. The truncated schatten p-norm approximates the rank function more closely than the nuclear norm, so the predictions are more accurate. We performed four different cross-validation experiments on two separate datasets, and TSPN outperformed various most advanced methods. In addition, public literature confirms a large number of predictive associations of TSPN in four case studies. Therefore, TSPN is a reliable model for SM–miRNA association prediction. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) is closely associated with human diseases. Accordingly, identifying the associations between human diseases and circRNA can help in disease prevention, diagnosis and treatment. Traditional methods are time consuming and laborious. Meanwhile, computational models can effectively predict potential circRNA–disease associations (CDAs), but are restricted by limited data, resulting in data with high dimension and imbalance. In this study, we propose a model based on automatically selected meta-path and contrastive learning, called the MPCLCDA model. First, the model constructs a new heterogeneous network based on circRNA similarity, disease similarity and known association, via automatically selected meta-path and obtains the low-dimensional fusion features of nodes via graph convolutional networks. Then, contrastive learning is used to optimize the fusion features further, and obtain the node features that make the distinction between positive and negative samples more evident. Finally, circRNA–disease scores are predicted through a multilayer perceptron. The proposed method is compared with advanced methods on four datasets. The average area under the receiver operating characteristic curve, area under the precision-recall curve and F1 score under 5-fold cross-validation reached 0.9752, 0.9831 and 0.9745, respectively. Simultaneously, case studies on human diseases further prove the predictive ability and application value of this method. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that metabolites are closely related to human diseases. Identifying disease-related metabolites is especially important for the diagnosis and treatment of disease. Previous works have mainly focused on the global topological information of metabolite and disease similarity networks. However, the local tiny structure of metabolites and diseases may have been ignored, leading to insufficiency and inaccuracy in the latent metabolite-disease interaction mining. Methods: To solve the aforementioned problem, we propose a novel metabolitedisease interaction prediction method with logical matrix factorization and local nearest neighbor constraints (LMFLNC). First, the algorithm constructs metabolitemetabolite and disease-disease similarity networks by integrating multi-source heterogeneous microbiome data. Then, the local spectral matrices based on these two networks are established and used as the input of the model, together with the known metabolite-disease interaction network. Finally, the probability of metabolite-disease interaction is calculated according to the learned latent representations of metabolites and diseases. Results: Extensive experiments on the metabolite-disease interaction data were conducted. The results show that the proposed LMFLNC method outperformed the second-best algorithm by 5.28 and 5.61% in the AUPR and F1, respectively. The LMFLNC method also exhibited several potential metabolite-disease interactions, such as “Cortisol” (HMDB0000063), relating to “21-Hydroxylase deficiency,” and “3-Hydroxybutyric acid” (HMDB0000011) and “Acetoacetic acid” (HMDB0000060), both relating to “3-Hydroxy-3-methylglutaryl-CoA lyase deficiency.” Conclusion: The proposed LMFLNC method can well preserve the geometrical structure of original data and can thus effectively predict the underlying associations between metabolites and diseases. The experimental results show its effectiveness in metabolite-disease interaction prediction. [ABSTRACT FROM AUTHOR]

Introduction: Exploring the potential efficacy of a drug is a valid approach for drug development with shorter development times and lower costs. Recently, several computational drug repositioning methods have been introduced to learn multifeatures for potential association prediction. However, fully leveraging the vast amount of information in the scientific literature to enhance drug-disease association prediction is a great challenge. Methods: We constructed a drug-disease association prediction method called Literature Based Multi-Feature Fusion (LBMFF), which effectively integrated known drugs, diseases, side effects and target associations from public databases as well as literature semantic features. Specifically, a pre-training and fine-tuning BERT model was introduced to extract literature semantic information for similarity assessment. Then, we revealed drug and disease embeddings from the constructed fusion similarity matrix by a graph convolutional network with an attention mechanism. Results: LBMFF achieved superior performance in drug-disease association prediction with an AUC value of 0.8818 and an AUPR value of 0.5916. Discussion: LBMFF achieved relative improvements of 31.67% and 16.09%, respectively, over the second-best results, compared to single feature methods and seven existing state-of-the-art prediction methods on the same test datasets. Meanwhile, case studies have verified that LBMFF can discover new associations to accelerate drug development. The proposed benchmark dataset and source code are available at: https://github.com/kang-hongyu/LBMFF. [ABSTRACT FROM AUTHOR]

Abstract Background Biological experiments have demonstrated that circRNA plays an essential role in various biological processes and human diseases. However, it is time-consuming and costly to merely conduct biological experiments to detect the association between circRNA and diseases. Accordingly, developing an efficient computational model to predict circRNA-disease associations is urgent. Methods In this research, we propose a multiple heterogeneous networks-based method, named XGBCDA, to predict circRNA-disease associations. The method first extracts original features, namely statistical features and graph theory features, from integrated circRNA similarity network, disease similarity network and circRNA-disease association network, and then sends these original features to the XGBoost classifier for training latent features. The method utilizes the tree learned by the XGBoost model, the index of leaf that instance finally falls into, and the 1 of K coding to represent the latent features. Finally, the method combines the latent features from the XGBoost with the original features to train the final model for predicting the association between the circRNA and diseases. Results The tenfold cross-validation results of the XGBCDA method illustrate that the area under the ROC curve reaches 0.9860. In addition, the method presents a striking performance in the case studies of colorectal cancer, gastric cancer and cervical cancer. Conclusion With fabulous performance in predicting potential circRNA-disease associations, the XGBCDA method has the promising ability to assist biomedical researchers in terms of circRNA-disease association prediction.

Exploring potential associations between small molecule drugs (SMs) and microRNAs (miRNAs) is significant for drug development and disease treatment. Since biological experiments are expensive and time-consuming, we propose a computational model based on accurate matrix completion for predicting potential SM–miRNA associations (AMCSMMA). Initially, a heterogeneous SM–miRNA network is constructed, and its adjacency matrix is taken as the target matrix. An optimization framework is then proposed to recover the target matrix with the missing values by minimizing its truncated nuclear norm, an accurate, robust, and efficient approximation to the rank function. Finally, we design an effective two-step iterative algorithm to solve the optimization problem and obtain the prediction scores. After determining the optimal parameters, we conduct four kinds of cross-validation experiments based on two datasets, and the results demonstrate that AMCSMMA is superior to the state-of-the-art methods. In addition, we implement another validation experiment, in which more evaluation metrics in addition to the AUC are introduced and finally achieve great results. In two types of case studies, a large number of SM–miRNA pairs with high predictive scores are confirmed by the published experimental literature. In summary, AMCSMMA has superior performance in predicting potential SM–miRNA associations, which can provide guidance for biological experiments and accelerate the discovery of new SM–miRNA associations. [ABSTRACT FROM AUTHOR]

With the high-quality development of bioinformatics technology, miRNA-disease associations (MDAs) are gradually being uncovered. At present, convenient and efficient prediction methods, which solve the problem of resource-consuming in traditional wet experiments, need to be further put forward. In this study, a space projection model based on block matrix is presented for predicting MDAs (BMPMDA). Specifically, two block matrices are first composed of the known association matrix and similarity to increase comprehensiveness. For the integrity of information in the heterogeneous network, matrix completion (MC) is utilized to mine potential MDAs. Considering the neighborhood information of data points, linear neighborhood similarity (LNS) is regarded as a measure of similarity. Next, LNS is projected onto the corresponding completed association matrix to derive the projection score. Finally, the AUC and AUPR values for BMPMDA reach 0.9691 and 0.6231, respectively. Additionally, the majority of novel MDAs in three disease cases are identified in existing databases and literature. It suggests that BMPMDA can serve as a reliable prediction model for biological research. [ABSTRACT FROM AUTHOR]

Numerous experimental studies have indicated that alteration and dysregulation in mircroRNAs (miRNAs) are associated with serious diseases. Identifying disease-related miRNAs is therefore an essential and challenging task in bioinformatics research. Computational methods are an efficient and economical alternative to conventional biomedical studies and can reveal underlying miRNA–disease associations for subsequent experimental confirmation with reasonable confidence. Despite the success of existing computational approaches, most of them only rely on the known miRNA–disease associations to predict associations without adding other data to increase the prediction accuracy, and they are affected by issues of data sparsity. In this paper, we present MRRN, a model that combines matrix reconstruction with node reliability to predict probable miRNA–disease associations. In MRRN, the most reliable neighbors of miRNA and disease are used to update the original miRNA–disease association matrix, which significantly reduces data sparsity. Unknown miRNA–disease associations are reconstructed by aggregating the most reliable first-order neighbors to increase prediction accuracy by representing the local and global structure of the heterogeneous network. Five-fold cross-validation of MRRN produced an area under the curve (AUC) of 0.9355 and area under the precision-recall curve (AUPR) of 0.2646, values that were greater than those produced by comparable models. Two different types of case studies using three diseases were conducted to demonstrate the accuracy of MRRN, and all top 30 predicted miRNAs were verified. [ABSTRACT FROM AUTHOR]

As microRNAs (miRNAs) are involved in many essential biological processes, their abnormal expressions can serve as biomarkers and prognostic indicators to prevent the development of complex diseases, thus providing accurate early detection and prognostic evaluation. Although a number of computational methods have been proposed to predict miRNA–disease associations (MDAs) for further experimental verification, their performance is limited primarily by the inadequacy of exploiting lower order patterns characterizing known MDAs to identify missing ones from MDA networks. Hence, in this work, we present a novel prediction model, namely HiSCMDA, by incorporating higher order network structures for improved performance of MDA prediction. To this end, HiSCMDA first integrates miRNA similarity network, disease similarity network and MDA network to preserve the advantages of all these networks. After that, it identifies overlapping functional modules from the integrated network by predefining several higher order connectivity patterns of interest. Last, a path-based scoring function is designed to infer potential MDAs based on network paths across related functional modules. HiSCMDA yields the best performance across all datasets and evaluation metrics in the cross-validation and independent validation experiments. Furthermore, in the case studies, 49 and 50 out of the top 50 miRNAs, respectively, predicted for colon neoplasms and lung neoplasms have been validated by well-established databases. Experimental results show that rich higher order organizational structures exposed in the MDA network gain new insight into the MDA prediction based on higher order connectivity patterns. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA)-disease association (MDA) prediction is critical for disease prevention, diagnosis, and treatment. Traditional MDA wet experiments, on the other hand, are inefficient and costly.Therefore, we proposed a multi-layer collaborative unsupervised training base model called SGAEMDA (Stacked Graph Autoencoder-Based Prediction of Potential miRNA-Disease Associations). First, from the original miRNA and disease data, we defined two types of initial features: similarity features and association features. Second, stacked graph autoencoder is then used to learn unsupervised low-dimensional representations of meaningful higher-order similarity features, and we concatenate the association features with the learned low-dimensional representations to obtain the final miRNA-disease pair features. Finally, we used a multilayer perceptron (MLP) to predict scores for unknown miRNA-disease associations. SGAEMDA achieved a mean area under the ROC curve of 0.9585 and 0.9516 in 5-fold and 10-fold cross-validation, which is significantly higher than the other baseline methods. Furthermore, case studies have shown that SGAEMDA can accurately predict candidate miRNAs for brain, breast, colon, and kidney neoplasms. [ABSTRACT FROM AUTHOR]

Abstract Background lncRNAs play a critical role in numerous biological processes and life activities, especially diseases. Considering that traditional wet experiments for identifying uncovered lncRNA-disease associations is limited in terms of time consumption and labor cost. It is imperative to construct reliable and efficient computational models as addition for practice. Deep learning technologies have been proved to make impressive contributions in many areas, but the feasibility of it in bioinformatics has not been adequately verified. Results In this paper, a machine learning-based model called LDACE was proposed to predict potential lncRNA-disease associations by combining Extreme Learning Machine (ELM) and Convolutional Neural Network (CNN). Specifically, the representation vectors are constructed by integrating multiple types of biology information including functional similarity and semantic similarity. Then, CNN is applied to mine both local and global features. Finally, ELM is chosen to carry out the prediction task to detect the potential lncRNA-disease associations. The proposed method achieved remarkable Area Under Receiver Operating Characteristic Curve of 0.9086 in Leave-one-out cross-validation and 0.8994 in fivefold cross-validation, respectively. In addition, 2 kinds of case studies based on lung cancer and endometrial cancer indicate the robustness and efficiency of LDACE even in a real environment. Conclusions Substantial results demonstrated that the proposed model is expected to be an auxiliary tool to guide and assist biomedical research, and the close integration of deep learning and biology big data will provide life sciences with novel insights.

MicroRNAs (miRNAs) are small RNA molecules consisting of approximately 22 nucleotides; they regulate gene expression and are employed in the development of therapeutics for intractable diseases. Predicting the association between miRNAs and genes is crucial for understanding their roles in molecular processes. miRNA–gene associations have been studied using deep learning methods, but these methods present various constraints. Through addressing the limitations of previous methods, this study aimed to achieve better performance than the state-of-the-art (SOTA) methods for studying miRNA–gene associations. We constructed the most extensive embedded dataset to date, comprising 717,728 miRNA–gene pairs, specifically designed for our deep learning model. Further, we applied an embedding method used for protein embedding for transforming our gene sequence data. Moreover, we constructed a sophisticated negative dataset based on three distance criteria, unlike most studies that randomly designate negative data. Leveraging the data and insights from these approaches, we built a deep learning model with the best performance among SOTA miRNA–gene studies (area under the receiver operating characteristic curve = 0.9834). In addition, we conducted a case study using the learned model to predict potential positive data. We also aimed to identify miRNAs closely associated with a gene linked to various cancers.

Long non-coding RNA (lncRNA) plays an important role in various complex human diseases.The development of effective prediction methods to infer the potential associations between lncRNA and diseases will not only help biologists understand the pathogenesis of diseases,but also contribute to the diagnosis,prevention,and treatment of human diseases.In this paper,an ensemble regression decision tree-based lncRNA-disease association method (ERDTLDA) is proposed to solve the lncRNA-disease association problem.First,ERDTLDA uses the open-source data of lncRNA to construct lncRNA,disease similarity matrix,lncRNA-disease association matrix respectively.Then,we obtain lncRNA,disease feature representations from these matrices.Principal component analysis is further exploited for feature extraction.Finally,a CART regression decision tree is used to yield association scores.An ensemble strategy for multiple decision trees is proposed to further improve the accuracy of our model.The results of LOOCV experiments show that the AUC of our method on three real lncRNA-disease datasets are 0.905 5,0.896 9 and 0.912 9 respectively,which are 6.46%,5.4% and 6.02% higher than the existing methods,respectively.Additionally,breast cancer,lung cancer,and gastric cancer are also used as case studies to further verify the accuracy and effectiveness of ERDTLDA.

Background: Biological experiments have demonstrated that circRNA plays an essential role in various biological processes and human diseases. However, it is time-consuming and costly to merely conduct biological experiments to detect the association between circRNA and diseases. Accordingly, developing an efficient computational model to predict circRNA-disease associations is urgent. Methods: In this research, we propose a multiple heterogeneous networks-based method, named XGBCDA, to predict circRNA-disease associations. The method first extracts original features, namely statistical features and graph theory features, from integrated circRNA similarity network, disease similarity network and circRNA-disease association network, and then sends these original features to the XGBoost classifier for training latent features. The method utilizes the tree learned by the XGBoost model, the index of leaf that instance finally falls into, and the 1 of K coding to represent the latent features. Finally, the method combines the latent features from the XGBoost with the original features to train the final model for predicting the association between the circRNA and diseases. Results: The tenfold cross-validation results of the XGBCDA method illustrate that the area under the ROC curve reaches 0.9860. In addition, the method presents a striking performance in the case studies of colorectal cancer, gastric cancer and cervical cancer. Conclusion: With fabulous performance in predicting potential circRNA-disease associations, the XGBCDA method has the promising ability to assist biomedical researchers in terms of circRNA-disease association prediction. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are closely related to a variety of human diseases, not only regulating gene expression, but also having an important role in human life activities and being viable targets of small molecule drugs for disease treatment. Current computational techniques to predict the potential associations between small molecule and miRNA are not that accurate. Here, we proposed a new computational method based on a deep autoencoder and a scalable tree boosting model (DAESTB), to predict associations between small molecule and miRNA. First, we constructed a high-dimensional feature matrix by integrating small molecule–small molecule similarity, miRNA–miRNA similarity and known small molecule–miRNA associations. Second, we reduced feature dimensionality on the integrated matrix using a deep autoencoder to obtain the potential feature representation of each small molecule–miRNA pair. Finally, a scalable tree boosting model is used to predict small molecule and miRNA potential associations. The experiments on two datasets demonstrated the superiority of DAESTB over various state-of-the-art methods. DAESTB achieved the best AUC value. Furthermore, in three case studies, a large number of predicted associations by DAESTB are confirmed with the public accessed literature. We envision that DAESTB could serve as a useful biological model for predicting potential small molecule–miRNA associations. [ABSTRACT FROM AUTHOR]

As space exploration programs progress, manned space missions will become more frequent and farther away from Earth, putting a greater emphasis on astronaut health. Through the collaborative efforts of researchers from various countries, the effect of the space environment factors on living systems is gradually being uncovered. Although a large number of interconnected research findings have been produced, their connection seems to be confused, and many unknown effects are left to be discovered. Simultaneously, several valuable data resources have emerged, accumulating data measuring biological effects in space that can be used to further investigate the unknown biological adaptations. In this review, the previous findings and their correlations are sorted out to facilitate the understanding of biological adaptations to space and the design of countermeasures. The biological effect measurement methods/data types are also organized to provide references for experimental design and data analysis. To aid deeper exploration of the data resources, we summarized common characteristics of the data generated from longitudinal experiments, outlined challenges or caveats in data analysis and provided corresponding solutions by recommending bioinformatics strategies and available models/tools. [ABSTRACT FROM AUTHOR]

Currently, there exist no generally accepted strategies of evaluating computational models for microRNA-disease associations (MDAs). Though K -fold cross validations and case studies seem to be must-have procedures, the value of K , the evaluation metrics, and the choice of query diseases as well as the inclusion of other procedures (such as parameter sensitivity tests, ablation studies and computational cost reports) are all determined on a case-by-case basis and depending on the researchers' choices. In the current review, we include a comprehensive analysis on how 29 state-of-the-art models for predicting MDAs were evaluated. Based on the analytical results, we recommend a feasible evaluation workflow that would suit any future model to facilitate fair and systematic assessment of predictive performance. [ABSTRACT FROM AUTHOR]

Computable models as a fundamental candidate for traditional biological experiments have been applied in inferring lncRNA-disease association (LDA) for many years, without time-consuming and laborious limitations. However, sparsity inherently existing in known heterogeneous bio-data is an obstacle to computable models to improve prediction accuracy further. Therefore, a new computational model composed of multiple mechanisms for lncRNA-disease association (MM-LDA) prediction was proposed, based on the fusion of the graph attention network (GAT) and inductive matrix completion (IMC). MM-LDA has two key steps to improve prediction accuracy: first, a multiple-operator aggregation was designed in the n-heads attention mechanism of the GAT. With this step, features of lncRNA nodes and disease nodes were enhanced. Second, IMC was introduced into the enhanced node features obtained in the first step, and then the LDA network was reconstructed to solve the cold start problem when data deficiency of the entire row or column happened in a known association matrix. Our MM-LDA achieved the following progress: first, using the Adam optimizer that adaptively adjusted the model learning rate could increase the convergent speed and not fall into local optima as well. Second, more excellent predictive ability was achieved against other similar models (with an AUC value of 0.9395 and an AUPR value of 0.8057 obtained from 5-fold cross-validation). Third, a 6.45% lower time cost was consumed against the advanced model GAMCLDA. In short, our MM-LDA achieved a more comprehensive prediction performance in terms of prediction accuracy and time cost. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that the regulation of long non-coding RNAs (lncRNAs) is closely related to a variety of diseases. Identifying meaningful lncRNA–disease associations will help to contribute to the understanding of the molecular mechanisms underlying these diseases. However, only a limited number of associations between lncRNAs and diseases have been inferred from traditional biological experiments due to the high cost and highly specialized. Therefore, computational methods are increasingly used to reduce time of biological experiments and complement biological research. In this paper, a computational method called HBRWRLDA is proposed to predict lncRNA–disease associations. First, HBRWRLDA models the relationships between multiple nodes using hypergraphs, which allows HBRWRLDA to integrate the expression similarity of lncRNAs and the semantic similarity of diseases to construct hypergraphs. Then, a bi-random walk on hypergraphs is used to predict potential lncRNA–disease associations. HBRWRLDA achieves a higher area under the curve value of 0.9551 and 0.9488 ± 0.0013 , respectively, compared with the other five advanced methods under the framework of one-leave cross validation (LOOCV) and five-fold cross-validation (5-fold CV). In addition, the prediction effect of HBRWRLDA was confirmed case studies of three diseases: renal cell carcinoma, gastric cancer, and hepatocellular carcinoma. Case studies demonstrates the capacity of HBRWRLDA to identify potentially disease-associated lncRNAs. Overall, HBRWRLDA is excellent at predicting potential lncRNA–disease associations and could be useful in conducting further biological experiments by helping researchers identify candidates of lncRNA–disease association. [ABSTRACT FROM AUTHOR]

• A computational method is proposed to calculate the relationship between microRNA and anticancer drugs sensitivity for the first time. • The light graph convolution network is constructed to obtain the high-order connection features from the microRNA-drug sensitivity relationship diagram, which effectively alleviates the over smoothing problem of the traditional graph convolution network. • Light graph convolution network discards the feature transformation and non-linear activation module in the traditional graph convolution network, only retains the most basic neighborhood aggregation, and has active generalization ability. Cancer has become one of the critical diseases threatening human life and health. The sensitivity difference of cancer drugs has always been a critical cause of the treatment come to nothing. Once drug resistance occurs, it will make the anticancer treatment or even various drugs ineffective. With the deepening of cancer research, a growing number of evidence shows that microRNA has a particular regulatory effect on the sensitivity of cancer drugs, which provides new research ideas. However, using traditional biological experiments to verify and discover the relations of microRNA-drug sensitivity is cumbersome and time-consuming, significantly slowing down cancer drug sensitivity's research progress. Therefore, this paper proposes a computational method (PDSM-LGCN) that spreads information through the high-order connection between cancer drug sensitivity and microRNA. At the same time, the model constructs an optimized-GCN as an embedding propagation layer to obtain the practical embeddings of microRNA and medicines. Finally, based on a collaborative filtering algorithm, the model brings the prediction score between microRNA and drug sensitivity. The results of fivefold cross-validation show that the AUC of PDSM-LGCN is 0.8872, and the AUPR is as high as 0.9026. At the same time, we also reproduced the five latest models of similar problems and compared the results. Our model has the best comprehensive effect among them. In addition, the reliability of PDSM-LGCN was further confirmed through the case study of Cisplatin and Doxorubicin, which can be used as a powerful tool for clinical and biological research. The source code and datasets can be obtained from https://github.com/19990915fzy/PDSM-LGCN/. [ABSTRACT FROM AUTHOR]

Predicting associations between microbes and diseases opens up new avenues for developing diagnostic, preventive, and therapeutic strategies. Given that laboratory-based biological tests to verify these associations are often time-consuming and expensive, there is a critical need for innovative computational frameworks to predict new microbe-disease associations. In this work, we introduce a novel prediction algorithm called Predicting Human Disease-Microbe Associations using Cross-Domain Matrix Factorization (CMFHMDA). Initially, we calculate the composite similarity of diseases and the Gaussian interaction profile similarity of microbes. We then apply the Weighted K Nearest Known Neighbors (WKNKN) algorithm to refine the microbe-disease association matrix. Our CMFHMDA model is subsequently developed by integrating the network data of both microbes and diseases to predict potential associations. The key innovations of this method include using the WKNKN algorithm to preprocess missing values in the association matrix and incorporating cross-domain information from microbes and diseases into the CMFHMDA model. To validate CMFHMDA, we employed three different cross-validation techniques to evaluate the model's accuracy. The results indicate that the CMFHMDA model achieved Area Under the Receiver Operating Characteristic Curve scores of 0.9172, 0.8551, and 0.9351$\pm $0.0052 in global Leave-One-Out Cross-Validation (LOOCV), local LOOCV, and five-fold CV, respectively. Furthermore, many predicted associations have been confirmed by published experimental studies, establishing CMFHMDA as an effective tool for predicting potential disease-associated microbes., (© The Author(s) 2024. Published by Oxford University Press.)

The accurate prediction of potential associations between microRNAs (miRNAs) and small molecule (SM) drugs can enhance our knowledge of how SM cures endogenous miRNA-related diseases. Given that traditional methods for predicting SM-miRNA associations are time-consuming and arduous, a number of computational models have been proposed to anticipate the potential SM–miRNA associations. However, several of these strategies failed to eliminate noise from the known SM-miRNA association information or failed to prioritize the most significant known SM-miRNA associations. Therefore, we proposed a model of Graph Convolutional Network with Layer Attention mechanism for SM-MiRNA Association prediction (GCNLASMMA). Firstly, we obtained the new SM-miRNA associations by matrix decomposition. The new SM-miRNA associations, as well as the integrated SM similarity and miRNA similarity were subsequently incorporated into a heterogeneous network. Finally, a graph convolutional network with an attention mechanism was used to compute the reconstructed SM-miRNA association matrix. Furthermore, four types of cross validations and two types of case studies were performed to assess the performance of GCNLASMMA. In cross validation, global Leave-One-Out Cross Validation (LOOCV), miRNA-fixed LOOCV, SM-fixed LOOCV and 5-fold cross-validation achieved excellent performance. Numerous hypothesized associations in case studies were confirmed by experimental literatures. All of these results confirmed that GCNLASMMA is a trustworthy association inference method.

Background. Efficient identification of microbe-drug associations is critical for drug development and solving problem of antimicrobial resistance. Traditional wet-lab method requires a lot of money and labor in identifying potential microbe-drug associations. With development of machine learning and publication of large amounts of biological data, computational methods become feasible. Methods. In this article, we proposed a computational model of neighborhood-based inference (NI) and restricted Boltzmann machine (RBM) to predict potential microbe-drug association (NIRBMMDA) by using integrated microbe similarity, integrated drug similarity and known microbe-drug associations. First, NI was used to obtain a score matrix of potential microbe-drug associations by using different thresholds to find similar neighbors for drug or microbe. Second, RBM was employed to obtain another score matrix of potential microbe-drug associations based on contrastive divergence algorithm and sigmoid function. Because generalization ability of individual method is poor, we used an ensemble learning to integrate two score matrices for predicting potential microbe-drug associations more accurately. In particular, NI can fully utilize similar (neighbor) information of drug or microbe and RBM can learn potential probability distribution hid in known microbe-drug associations. Moreover, ensemble learning was used to integrate individual predictor for obtaining a stronger predictor. Results. In global leave-one-out cross validation (LOOCV), NIRBMMDA gained the area under the receiver operating characteristics curve (AUC) of 0.8666, 0.9413 and 0.9557 for datasets of DrugVirus, MDAD and aBiofilm, respectively. In local LOOCV, AUCs of 0.8512, 0.9204 and 0.9414 were obtained for NIRBMMDA based on datasets of DrugVirus, MDAD and aBiofilm, respectively. For five-fold cross validation, NIRBMMDA acquired AUC and standard deviation of 0.8569 ± -0.0027, 0.9248 ± -0.0014 and 0.9369 ± -0.0020 on the basis of datasets of DrugVirus, MDAD and aBiofilm, respectively. Moreover, case study for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed that 13 out of the top 20 predicted drugs were verified by searching literature. The other two case studies indicated that 17 and 17 out of the top 20 predicted microbes for the drug of ciprofloxacin and minocycline were confirmed by identifying published literature, respectively. [ABSTRACT FROM AUTHOR]

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Amid the COVID‐19 crisis, we put sizeable efforts to collect a high number of experimentally validated drug–virus association entries from literature by text mining and built a human drug–virus association database. To the best of our knowledge, it is the largest publicly available drug–virus database so far. Next, we develop a novel weight regularization matrix factorization approach, termed WRMF, for in silico drug repurposing by integrating three networks: the known drug–virus association network, the drug–drug chemical structure similarity network, and the virus–virus genomic sequencing similarity network. Specifically, WRMF adds a weight to each training sample for reducing the influence of negative samples (i.e. the drug–virus association is unassociated). A comparison on the curated drug–virus database shows that WRMF performs better than a few state‐of‐the‐art methods. In addition, we selected the other two different public datasets (i.e. Cdataset and HMDD V2.0) to assess WRMF's performance. The case study also demonstrated the accuracy and reliability of WRMF to infer potential drugs for the novel virus. In summary, we offer a useful tool including a novel drug–virus association database and a powerful method WRMF to repurpose potential drugs for new viruses. [ABSTRACT FROM AUTHOR]

Abstract Background Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential. Results Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611. Conclusions We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.

Growing evidence has elucidated that long non-coding RNAs (lncRNAs) are involved in a variety of complex diseases in human bodies. In recent years, it has become a hot topic to develop effective computational models to identify potential lncRNA-disease associations. In this article, a novel method called ICLRBBN (Internal Confidence-Based Local Radial Basis Biological Network) is proposed to detect potential lncRNA-disease associations by adopting an internal confidence-based radial basis biological network. In ICLRBBN, a novel internal confidence-based collaborative filtering recommendation algorithm was designed first to mine hidden features between lncRNAs and diseases, which guarantees that ICLRBBN can be more effectively applied to predict new diseases. Then, a unique three-layer local radial basis function network consisting of diseases and lncRNAs was constructed, based on which the association probability between diseases and lncRNAs was calculated by combining different characteristics of lncRNAs with local information of diseases. Finally, we compared ICLRBBN with 6 state-of-the-art methods based on two different validation frameworks. Simulation results showed that area under the receiver operating characteristic curve (AUC) values achieved by ICLRBBN outperformed all competing methods. Furthermore, case studies illustrated that ICLRBBN has a promising future as a powerful tool in the practical application of lncRNA-disease association prediction. A web service for prediction of potential lncRNA-disease associations is available at http://leelab2997.cn/.

Exploring potential associations between small molecule drugs (SMs) and microRNAs (miRNAs) is significant for drug development and disease treatment. Since biological experiments are expensive and time-consuming, we propose a computational model based on accurate matrix completion for predicting potential SM–miRNA associations (AMCSMMA). Initially, a heterogeneous SM–miRNA network is constructed, and its adjacency matrix is taken as the target matrix. An optimization framework is then proposed to recover the target matrix with the missing values by minimizing its truncated nuclear norm, an accurate, robust, and efficient approximation to the rank function. Finally, we design an effective two-step iterative algorithm to solve the optimization problem and obtain the prediction scores. After determining the optimal parameters, we conduct four kinds of cross-validation experiments based on two datasets, and the results demonstrate that AMCSMMA is superior to the state-of-the-art methods. In addition, we implement another validation experiment, in which more evaluation metrics in addition to the AUC are introduced and finally achieve great results. In two types of case studies, a large number of SM–miRNA pairs with high predictive scores are confirmed by the published experimental literature. In summary, AMCSMMA has superior performance in predicting potential SM–miRNA associations, which can provide guidance for biological experiments and accelerate the discovery of new SM–miRNA associations.

Motivation Identifying disease-related genes is an important issue in computational biology. Module structure widely exists in biomolecule networks, and complex diseases are usually thought to be caused by perturbations of local neighborhoods in the networks, which can provide useful insights for the study of disease-related genes. However, the mining and effective utilization of the module structure is still challenging in such issues as a disease gene prediction. Results We propose a hybrid disease-gene prediction method integrating multiscale module structure (HyMM), which can utilize multiscale information from local to global structure to more effectively predict disease-related genes. HyMM extracts module partitions from local to global scales by multiscale modularity optimization with exponential sampling, and estimates the disease relatedness of genes in partitions by the abundance of disease-related genes within modules. Then, a probabilistic model for integration of gene rankings is designed in order to integrate multiple predictions derived from multiscale module partitions and network propagation, and a parameter estimation strategy based on functional information is proposed to further enhance HyMM's predictive power. By a series of experiments, we reveal the importance of module partitions at different scales, and verify the stable and good performance of HyMM compared with eight other state-of-the-arts and its further performance improvement derived from the parameter estimation. Conclusions The results confirm that HyMM is an effective framework for integrating multiscale module structure to enhance the ability to predict disease-related genes, which may provide useful insights for the study of the multiscale module structure and its application in such issues as a disease-gene prediction. [ABSTRACT FROM AUTHOR]

With an in-depth understanding of noncoding ribonucleic acid (RNA), many studies have shown that microRNA (miRNA) plays an important role in human diseases. Because traditional biological experiments are time-consuming and laborious, new calculation methods have recently been developed to predict associations between miRNA and diseases. In this review, we collected various miRNA–disease association prediction models proposed in recent years and used two common data sets to evaluate the performance of the prediction models. First, we systematically summarized the commonly used databases and similarity data for predicting miRNA–disease associations, and then divided the various calculation models into four categories for summary and detailed introduction. In this study, two independent datasets (D 5430 and D 6088) were compiled to systematically evaluate 11 publicly available prediction tools for miRNA–disease associations. The experimental results indicate that the methods based on information dissemination and the method based on scoring function require shorter running time. The method based on matrix transformation often requires a longer running time, but the overall prediction result is better than the previous two methods. We hope that the summary of work related to miRNA and disease will provide comprehensive knowledge for predicting the relationship between miRNA and disease and contribute to advanced computation tools in the future. [ABSTRACT FROM AUTHOR]

Background: lncRNAs play a critical role in numerous biological processes and life activities, especially diseases. Considering that traditional wet experiments for identifying uncovered lncRNA-disease associations is limited in terms of time consumption and labor cost. It is imperative to construct reliable and efficient computational models as addition for practice. Deep learning technologies have been proved to make impressive contributions in many areas, but the feasibility of it in bioinformatics has not been adequately verified. Results: In this paper, a machine learning-based model called LDACE was proposed to predict potential lncRNA-disease associations by combining Extreme Learning Machine (ELM) and Convolutional Neural Network (CNN). Specifically, the representation vectors are constructed by integrating multiple types of biology information including functional similarity and semantic similarity. Then, CNN is applied to mine both local and global features. Finally, ELM is chosen to carry out the prediction task to detect the potential lncRNA-disease associations. The proposed method achieved remarkable Area Under Receiver Operating Characteristic Curve of 0.9086 in Leave-one-out cross-validation and 0.8994 in fivefold cross-validation, respectively. In addition, 2 kinds of case studies based on lung cancer and endometrial cancer indicate the robustness and efficiency of LDACE even in a real environment. Conclusions: Substantial results demonstrated that the proposed model is expected to be an auxiliary tool to guide and assist biomedical research, and the close integration of deep learning and biology big data will provide life sciences with novel insights. [ABSTRACT FROM AUTHOR]

Extensive clinical and biomedical studies have shown that microbiome plays a prominent role in human health. Identifying potential microbe–disease associations (MDAs) can help reveal the pathological mechanism of human diseases and be useful for the prevention, diagnosis, and treatment of human diseases. Therefore, it is necessary to develop effective computational models and reduce the cost and time of biological experiments. Here, we developed a novel machine learning-based joint framework called CWNMF-GLapRLS for human MDA prediction using the proposed collaborative weighted non-negative matrix factorization (CWNMF) technique and graph Laplacian regularized least squares. Especially, to fuse more similarity information, we calculated the functional similarity of microbes. To deal with missing values and effectively overcome the data sparsity problem, we proposed a collaborative weighted NMF technique to reconstruct the original association matrix. In addition, we developed a graph Laplacian regularized least-squares method for prediction. The experimental results of fivefold and leave-one-out cross-validation demonstrated that our method achieved the best performance by comparing it with 5 state-of-the-art methods on the benchmark dataset. Case studies further showed that the proposed method is an effective tool to predict potential MDAs and can provide more help for biomedical researchers. [ABSTRACT FROM AUTHOR]

In recent years, increasing biological experiments and scientific studies have demonstrated that microRNA (miRNA) plays an important role in the development of human complex diseases. Therefore, discovering miRNA–disease associations can contribute to accurate diagnosis and effective treatment of diseases. Identifying miRNA–disease associations through computational methods based on biological data has been proven to be low-cost and high-efficiency. In this study, we proposed a computational model named Stacked Autoencoder for potential MiRNA–Disease Association prediction (SAEMDA). In SAEMDA, all the miRNA–disease samples were used to pretrain a Stacked Autoencoder (SAE) in an unsupervised manner. Then, the positive samples and the same number of selected negative samples were utilized to fine-tune SAE in a supervised manner after adding an output layer with softmax classifier to the SAE. SAEMDA can make full use of the feature information of all unlabeled miRNA–disease pairs. Therefore, SAEMDA is suitable for our dataset containing small labeled samples and large unlabeled samples. As a result, SAEMDA achieved AUCs of 0.9210 and 0.8343 in global and local leave-one-out cross validation. Besides, SAEMDA obtained an average AUC and standard deviation of 0.9102 ± /−0.0029 in 100 times of 5-fold cross validation. These results were better than those of previous models. Moreover, we carried out three case studies to further demonstrate the predictive accuracy of SAEMDA. As a result, 82% (breast neoplasms), 100% (lung neoplasms) and 90% (esophageal neoplasms) of the top 50 predicted miRNAs were verified by databases. Thus, SAEMDA could be a useful and reliable model to predict potential miRNA–disease associations. [ABSTRACT FROM AUTHOR]

Since miRNAs can participate in the posttranscriptional regulation of gene expression, they may provide ideas for the development of new drugs or become new biomarkers for drug targets or disease diagnosis. In this work, we propose an miRNA–disease association prediction method based on meta-paths (MDPBMP). First, an miRNA–disease–gene heterogeneous information network was constructed, and seven symmetrical meta-paths were defined according to different semantics. After constructing the initial feature vector for the node, the vector information carried by all nodes on the meta-path instance is extracted and aggregated to update the feature vector of the starting node. Then, the vector information obtained by the nodes on different meta-paths is aggregated. Finally, miRNA and disease embedding feature vectors are used to calculate their associated scores. Compared with the other methods, MDPBMP obtained the highest AUC value of 0.9214. Among the top 50 predicted miRNAs for lung neoplasms, esophageal neoplasms, colon neoplasms and breast neoplasms, 49, 48, 49 and 50 have been verified. Furthermore, for breast neoplasms, we deleted all the known associations between breast neoplasms and miRNAs from the training set. These results also show that for new diseases without known related miRNA information, our model can predict their potential miRNAs. Code and data are available at https://github.com/LiangYu-Xidian/MDPBMP. [ABSTRACT FROM AUTHOR]