A deep ensemble model to predict miRNA-disease association.
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ABSTRACT:
SUBMITTER: Fu L
PROVIDER: S-EPMC5670180 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
Publications
A deep ensemble model to predict miRNA-disease association.
Scientific reports 20171103 1
Cumulative evidence from biological experiments has confirmed that microRNAs (miRNAs) are related to many types of human diseases through different biological processes. It is anticipated that precise miRNA-disease association prediction could not only help infer potential disease-related miRNA but also boost human diagnosis and disease prevention. Considering the limitations of previous computational models, a more effective computational model needs to be implemented to predict miRNA-disease a ...[more]
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Project description:Recently, accumulating evidences have indicated miRNAs play critical roles in the progression and development of various human complex diseases, which pointed out that identifying miRNA-disease association could enable us to understand diseases at miRNA level. Thus, revealing more and more potential miRNA-disease associations is a vital topic in biomedical domain. However, it will be extremely expensive and time-consuming if we examine all the possible miRNA-disease pairs. Therefore, more accurate and efficient methods are being highly requested to detect potential miRNA-disease associations. In this study, we developed a computational model of Ensemble Learning and Link Prediction for miRNA-Disease Association prediction (ELLPMDA) to achieve this goal. By integrating miRNA functional similarity, disease semantic similarity, miRNA-disease association and Gaussian profile kernel similarity for miRNAs and diseases, we constructed a similarity network and utilized ensemble learning to combine rank results given by three classic similarity-based algorithms. To evaluate the performance of ELLPMDA, we exploited global and local Leave-One-Out Cross Validation (LOOCV), 5-fold Cross Validation (CV) and three kinds of case studies. As a result, the AUCs of ELLPMDA is 0.9181, 0.8181 and 0.9193+/-0.0002 in global LOOCV, local LOOCV and 5-fold CV, respectively, which significantly exceed almost all the previous methods. Moreover, in three distinct kinds of case studies for Kidney Neoplasms, Lymphoma, Prostate Neoplasms, Colon Neoplasms and Esophageal Neoplasms, 88%, 92%, 86%, 98% and 98% out of the top 50 predicted miRNAs has been confirmed, respectively. Besides, ELLPMDA is based on global similarity measure and applicable to new diseases without any known related miRNAs.
| S-EPMC6152467 | biostudies-literature
Project description:Recently, microRNAs (miRNAs) are confirmed to be important molecules within many crucial biological processes and therefore related to various complex human diseases. However, previous methods of predicting miRNA-disease associations have their own deficiencies. Under this circumstance, we developed a prediction method called deep representations-based miRNA-disease association (DRMDA) prediction. The original miRNA-disease association data were extracted from HDMM database. Meanwhile, stacked auto-encoder, greedy layer-wise unsupervised pre-training algorithm and support vector machine were implemented to predict potential associations. We compared DRMDA with five previous classical prediction models (HGIMDA, RLSMDA, HDMP, WBSMDA and RWRMDA) in global leave-one-out cross-validation (LOOCV), local LOOCV and fivefold cross-validation, respectively. The AUCs achieved by DRMDA were 0.9177, 08339 and 0.9156 ± 0.0006 in the three tests above, respectively. In further case studies, we predicted the top 50 potential miRNAs for colon neoplasms, lymphoma and prostate neoplasms, and 88%, 90% and 86% of the predicted miRNA can be verified by experimental evidence, respectively. In conclusion, DRMDA is a promising prediction method which could identify potential and novel miRNA-disease associations.
| S-EPMC5742725 | biostudies-literature
Project description:BackgroundCumulative evidence from biological experiments has confirmed that miRNAs have significant roles to diagnose and treat complex diseases. However, traditional medical experiments have limitations in time-consuming and high cost so that they fail to find the unconfirmed miRNA and disease interactions. Thus, discovering potential miRNA-disease associations will make a contribution to the decrease of the pathogenesis of diseases and benefit disease therapy. Although, existing methods using different computational algorithms have favorable performances to search for the potential miRNA-disease interactions. We still need to do some work to improve experimental results.ResultsWe present a novel combined embedding model to predict MiRNA-disease associations (CEMDA) in this article. The combined embedding information of miRNA and disease is composed of pair embedding and node embedding. Compared with the previous heterogeneous network methods that are merely node-centric to simply compute the similarity of miRNA and disease, our method fuses pair embedding to pay more attention to capturing the features behind the relative information, which models the fine-grained pairwise relationship better than the previous case when each node only has a single embedding. First, we construct the heterogeneous network from supported miRNA-disease pairs, disease semantic similarity and miRNA functional similarity. Given by the above heterogeneous network, we find all the associated context paths of each confirmed miRNA and disease. Meta-paths are linked by nodes and then input to the gate recurrent unit (GRU) to directly learn more accurate similarity measures between miRNA and disease. Here, the multi-head attention mechanism is used to weight the hidden state of each meta-path, and the similarity information transmission mechanism in a meta-path of miRNA and disease is obtained through multiple network layers. Second, pair embedding of miRNA and disease is fed to the multi-layer perceptron (MLP), which focuses on more important segments in pairwise relationship. Finally, we combine meta-path based node embedding and pair embedding with the cost function to learn and predict miRNA-disease association. The source code and data sets that verify the results of our research are shown at https://github.com/liubailong/CEMDA .ConclusionsThe performance of CEMDA in the leave-one-out cross validation and fivefold cross validation are 93.16% and 92.03%, respectively. It denotes that compared with other methods, CEMDA accomplishes superior performance. Three cases with lung cancers, breast cancers, prostate cancers and pancreatic cancers show that 48,50,50 and 50 out of the top 50 miRNAs, which are confirmed in HDMM V2.0. Thus, this further identifies the feasibility and effectiveness of our method.
| S-EPMC7995599 | biostudies-literature
Project description:BackgroundUnified Parkinson Disease Rating Scale-part III (UPDRS III) is part of the standard clinical examination performed to track the severity of Parkinson's disease (PD) motor complications. Wearable technologies could be used to reduce the need for on-site clinical examinations of people with Parkinson's disease (PwP) and provide a reliable and continuous estimation of the severity of PD at home. The reported estimation can be used to successfully adjust the dose and interval of PD medications.MethodsWe developed a novel algorithm for unobtrusive and continuous UPDRS-III estimation at home using two wearable inertial sensors mounted on the wrist and ankle. We used the ensemble of three deep-learning models to detect UPDRS-III-related patterns from a combination of hand-crafted features, raw temporal signals, and their time-frequency representation. Specifically, we used a dual-channel, Long Short-Term Memory (LSTM) for hand-crafted features, 1D Convolutional Neural Network (CNN)-LSTM for raw signals, and 2D CNN-LSTM for time-frequency data. We utilized transfer learning from activity recognition data and proposed a two-stage training for the CNN-LSTM networks to cope with the limited amount of data.ResultsThe algorithm was evaluated on gyroscope data from 24 PwP as they performed different daily living activities. The estimated UPDRS-III scores had a correlation of [Formula: see text] and a mean absolute error of 5.95 with the clinical examination scores without requiring the patients to perform any specific tasks.ConclusionOur analysis demonstrates the potential of our algorithm for estimating PD severity scores unobtrusively at home. Such an algorithm could provide the required motor-complication measurements without unnecessary clinical visits and help the treating physician provide effective management of the disease.
| S-EPMC8010504 | biostudies-literature
Project description:Many epidemics have afflicted humanity throughout history, claiming many lives. It has been noted in our time that heart disease is one of the deadliest diseases that humanity has confronted in the contemporary period. The proliferation of poor habits such as smoking, overeating, and lack of physical activity has contributed to the rise in heart disease. The killing feature of heart disease, which has earned it the moniker the "silent killer," is that it frequently has no apparent signs in advance. As a result, research is required to develop a promising model for the early identification of heart disease using simple data and symptoms. The paper's aim is to propose a deep stacking ensemble model to enhance the performance of the prediction of heart disease. The proposed ensemble model integrates two optimized and pre-trained hybrid deep learning models with the Support Vector Machine (SVM) as the meta-learner model. The first hybrid model is Convolutional Neural Network (CNN)-Long Short-Term Memory (LSTM) (CNN-LSTM), which integrates CNN and LSTM. The second hybrid model is CNN-GRU, which integrates CNN with a Gated Recurrent Unit (GRU). Recursive Feature Elimination (RFE) is also used for the feature selection optimization process. The proposed model has been optimized and tested using two different heart disease datasets. The proposed ensemble is compared with five machine learning models including Logistic Regression (LR), Random Forest (RF), K-Nearest Neighbors (K-NN), Decision Tree (DT), Naïve Bayes (NB), and hybrid models. In addition, optimization techniques are used to optimize ML, DL, and the proposed models. The results obtained by the proposed model achieved the highest performance using the full feature set.
| S-EPMC9777370 | biostudies-literature
Project description:Oppositional defiant disorder and conduct disorder, collectively referred to as disruptive behavior disorders (DBDs), are prevalent psychiatric disorders in children. Early diagnosis of DBDs is crucial because they can increase the risks of other mental health and substance use disorders without appropriate psychosocial interventions and treatment. However, diagnosing DBDs is challenging as they are often comorbid with other disorders, such as attention-deficit/hyperactivity disorder, anxiety, and depression. In this study, a multimodal ensemble three-dimensional convolutional neural network (3D CNN) deep learning model was used to classify children with DBDs and typically developing children. The study participants included 419 females and 681 males, aged 108-131 months who were enrolled in the Adolescent Brain Cognitive Development Study. Children were grouped based on the presence of DBDs (n = 550) and typically developing (n = 550); assessments were based on the scores from the Child Behavior Checklist and on the Schedule for Affective Disorders and Schizophrenia for School-age Children-Present and Lifetime version for DSM-5. The diffusion, structural, and resting-state functional magnetic resonance imaging (rs-fMRI) data were used as input data to the 3D CNN. The model achieved 72% accuracy in classifying children with DBDs with 70% sensitivity, 72% specificity, and an F1-score of 70. In addition, the discriminative power of the classifier was investigated by identifying the cortical and subcortical regions primarily involved in the prediction of DBDs using a gradient-weighted class activation mapping method. The classification results were compared with those obtained using the three neuroimaging modalities individually, and a connectome-based graph CNN and a multi-scale recurrent neural network using only the rs-fMRI data.
| S-EPMC8652047 | biostudies-literature
Project description:In recent years, increasing associations between microRNAs (miRNAs) and human diseases have been identified. Based on accumulating biological data, many computational models for potential miRNA-disease associations inference have been developed, which saves time and expenditure on experimental studies, making great contributions to researching molecular mechanism of human diseases and developing new drugs for disease treatment. In this paper, we proposed a novel computational method named Ensemble of Decision Tree based MiRNA-Disease Association prediction (EDTMDA), which innovatively built a computational framework integrating ensemble learning and dimensionality reduction. For each miRNA-disease pair, the feature vector was extracted by calculating the statistical measures, graph theoretical measures, and matrix factorization results for the miRNA and disease, respectively. Then multiple base learnings were built to yield many decision trees (DTs) based on random selection of negative samples and miRNA/disease features. Particularly, Principal Components Analysis was applied to each base learning to reduce feature dimensionality and hence remove the noise or redundancy. Average strategy was adopted for these DTs to get final association scores between miRNAs and diseases. In model performance evaluation, EDTMDA showed AUC of 0.9309 in global leave-one-out cross validation (LOOCV) and AUC of 0.8524 in local LOOCV. Additionally, AUC of 0.9192+/-0.0009 in 5-fold cross validation proved the model's reliability and stability. Furthermore, three types of case studies for four human diseases were implemented. As a result, 94% (Esophageal Neoplasms), 86% (Kidney Neoplasms), 96% (Breast Neoplasms) and 88% (Carcinoma Hepatocellular) of top 50 predicted miRNAs were confirmed by experimental evidences in literature.
| S-EPMC6675125 | biostudies-literature
Project description:As increasing experimental studies have shown that microRNAs (miRNAs) are closely related to multiple biological processes and the prevention, diagnosis and treatment of human diseases, a growing number of researchers are focusing on the identification of associations between miRNAs and diseases. Identifying such associations purely via experiments is costly and demanding, which prompts researchers to develop computational methods to complement the experiments. In this paper, a novel prediction model named Ensemble of Kernel Ridge Regression based MiRNA-Disease Association prediction (EKRRMDA) was developed. EKRRMDA obtained features of miRNAs and diseases by integrating the disease semantic similarity, the miRNA functional similarity and the Gaussian interaction profile kernel similarity for diseases and miRNAs. Under the computational framework that utilized ensemble learning and feature dimensionality reduction, multiple base classifiers that combined two Kernel Ridge Regression classifiers from the miRNA side and disease side, respectively, were obtained based on random selection of features. Then average strategy for these base classifiers was adopted to obtain final association scores of miRNA-disease pairs. In the global and local leave-one-out cross validation, EKRRMDA attained the AUCs of 0.9314 and 0.8618, respectively. Moreover, the model's average AUC with standard deviation in 5-fold cross validation was 0.9275 ± 0.0008. In addition, we implemented three different types of case studies on predicting miRNAs associated with five important diseases. As a result, there were 90% (Esophageal Neoplasms), 86% (Kidney Neoplasms), 86% (Lymphoma), 98% (Lung Neoplasms), and 96% (Breast Neoplasms) of the top 50 predicted miRNAs verified to have associations with these diseases.
| S-EPMC7015868 | biostudies-literature
Project description:Recently, an increasing number of studies have demonstrated that miRNAs are involved in human diseases, indicating that miRNAs might be a potential pathogenic factor for various diseases. Therefore, figuring out the relationship between miRNAs and diseases plays a critical role in not only the development of new drugs, but also the formulation of individualized diagnosis and treatment. As the prediction of miRNA-disease association via biological experiments is expensive and time-consuming, computational methods have a positive effect on revealing the association. In this study, a novel prediction model integrating GCN, CNN and Squeeze-and-Excitation Networks (GCSENet) was constructed for the identification of miRNA-disease association. The model first captured features by GCN based on a heterogeneous graph including diseases, genes and miRNAs. Then, considering the different effects of genes on each type of miRNA and disease, as well as the different effects of the miRNA-gene and disease-gene relationships on miRNA-disease association, a feature weight was set and a combination of miRNA-gene and disease-gene associations was added as feature input for the convolution operation in CNN. Furthermore, the squeeze and excitation blocks of SENet were applied to determine the importance of each feature channel and enhance useful features by means of the attention mechanism, thus achieving a satisfactory prediction of miRNA-disease association. The proposed method was compared against other state-of-the-art methods. It achieved an AUROC score of 95.02% and an AUPR score of 95.55% in a 10-fold cross-validation, which led to the finding that the proposed method is superior to these popular methods on most of the performance evaluation indexes.
| S-EPMC8205154 | biostudies-literature
Project description:BackgroundMiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction.ResultsWe developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model.ConclusionsDNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/ .
| S-EPMC10785389 | biostudies-literature