KSIMC: Predicting Kinase⁻Substrate Interactions Based on Matrix Completion.
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ABSTRACT:
SUBMITTER: Gan J
PROVIDER: S-EPMC6358935 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Predicting the interactions between drugs and targets plays an important role in the process of new drug discovery, drug repurposing (also known as drug repositioning). There is a need to develop novel and efficient prediction approaches in order to avoid the costly and laborious process of determining drug-target interactions (DTIs) based on experiments alone. These computational prediction approaches should be capable of identifying the potential DTIs in a timely manner. Matrix factorization methods have been proven to be the most reliable group of methods. Here, we first propose a matrix factorization-based method termed 'Coupled Matrix-Matrix Completion' (CMMC). Next, in order to utilize more comprehensive information provided in different databases and incorporate multiple types of scores for drug-drug similarities and target-target relationship, we then extend CMMC to 'Coupled Tensor-Matrix Completion' (CTMC) by considering drug-drug and target-target similarity/interaction tensors. Results: Evaluation on two benchmark datasets, DrugBank and TTD, shows that CTMC outperforms the matrix-factorization-based methods: GRMF, $L_{2,1}$-GRMF, NRLMF and NRLMF$\beta $. Based on the evaluation, CMMC and CTMC outperform the above three methods in term of area under the curve, F1 score, sensitivity and specificity in a considerably shorter run time.
| S-EPMC7986629 | biostudies-literature
Project description: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.
| S-EPMC10137058 | biostudies-literature
Project description:Identification of potential drug-associated indications is critical for either approved or novel drugs in drug repositioning. Current computational methods based on drug similarity and disease similarity have been developed to predict drug-disease associations. When more reliable drug- or disease-related information becomes available and is integrated, the prediction precision can be continuously improved. However, it is a challenging problem to effectively incorporate multiple types of prior information, representing different characteristics of drugs and diseases, to identify promising drug-disease associations. In this study, we propose an overlap matrix completion (OMC) for bilayer networks (OMC2) and tri-layer networks (OMC3) to predict potential drug-associated indications, respectively. OMC is able to efficiently exploit the underlying low-rank structures of the drug-disease association matrices. In OMC2, first of all, we construct one bilayer network from drug-side aspect and one from disease-side aspect, and then obtain their corresponding block adjacency matrices. We then propose the OMC2 algorithm to fill out the values of the missing entries in these two adjacency matrices, and predict the scores of unknown drug-disease pairs. Moreover, we further extend OMC2 to OMC3 to handle tri-layer networks. Computational experiments on various datasets indicate that our OMC methods can effectively predict the potential drug-disease associations. Compared with the other state-of-the-art approaches, our methods yield higher prediction accuracy in 10-fold cross-validation and de novo experiments. In addition, case studies also confirm the effectiveness of our methods in identifying promising indications for existing drugs in practical applications.
| S-EPMC6946175 | biostudies-literature
Project description:Protein kinases become an important source of potential drug targets. Developing new, efficient, and safe small-molecule kinase inhibitors has become an important topic in the field of drug research and development. In contrast with traditional wet experiments which are time-consuming and expensive, machine learning-based approaches for predicting small molecule inhibitors for protein kinases are time-saving and cost-effective, which are highly desired for us. However, the issue of sample scarcity (known active and inactive compounds are usually limited for most kinases) poses a challenge to the research and development of machine learning-based kinase inhibitors' active prediction methods. To alleviate the data scarcity problem in the prediction of kinase inhibitors, in this study, we present a novel Meta-learning-based inductive logistic matrix completion method for the Prediction of Kinase Inhibitors (MetaILMC). MetaILMC adopts a meta-learning framework to learn a well-generalized model from tasks with sufficient samples, which can fast adapt to new tasks with limited samples. As MetaILMC allows the effective transfer of the prior knowledge learned from kinases with sufficient samples to kinases with a small number of samples, the proposed model can produce accurate predictions for kinases with limited data. Experimental results show that MetaILMC has excellent performance for prediction tasks of kinases with few-shot samples and is significantly superior to the state-of-the-art multi-task learning in terms of AUC, AUPR, etc., various performance metrics. Case studies also provided for two drugs to predict Kinase Inhibitory scores, further validating the proposed method's effectiveness and feasibility. SCIENTIFIC CONTRIBUTION: Considering the potential correlation between activity prediction tasks for different kinases, we propose a novel meta learning algorithm MetaILMC, which learns a prior of strong generalization capacity during meta-training from the tasks with sufficient training samples, such that it can be easily and quickly adapted to the new tasks of the kinase with scarce data during meta-testing. Thus, MetaILMC can effectively alleviate the data scarcity problem in the prediction of kinase inhibitors.
| S-EPMC11301988 | biostudies-literature
Project description:The rapid mutation of influenza viruses especially on the two surface proteins hemagglutinin (HA) and neuraminidase (NA) has made them capable to escape from population immunity, which has become a key challenge for influenza vaccine design. Thus, it is crucial to predict influenza antigenic evolution and identify new antigenic variants in a timely manner. However, traditional experimental methods like hemagglutination inhibition (HI) assay to select vaccine strains are time and labor-intensive, while popular computational methods are less sensitive, which presents the need for more accurate algorithms. In this study, we have proposed a novel low-rank matrix completion model MCAAS to infer antigenic distances between antigens and antisera based on partially revealed antigenic distances, virus similarity based on HA protein sequences, and vaccine similarity based on vaccine strains. The model exploits the correlations of viruses and vaccines in serological tests as well as the ability of HAs from viruses and vaccine strains in inferring influenza antigenicity. We also compared the effects of comprehensive 65 amino acids substitution matrices in predicting influenza antigenicity. As a result, we applied MCAAS into H3N2 seasonal influenza virus data. Our model achieved a 10-fold cross validation root-mean-squared error (RMSE) of 0.5982, significantly outperformed existing computational methods like antigenic cartography, AntigenMap and BMCSI. We also constructed the antigenic map and studied the association between genetic and antigenic evolution of H3N2 influenza viruses. Finally, our analyses showed that homologous structure derived amino acid substitution matrix (HSDM) is most powerful in predicting influenza antigenicity, which is consistent with previous studies.
| S-EPMC6206390 | biostudies-literature
Project description:Many studies have clarified that microRNAs (miRNAs) are associated with many human diseases. Therefore, it is essential to predict potential miRNA-disease associations for disease pathogenesis and treatment. Numerous machine learning and deep learning approaches have been adopted to this problem. In this paper, we propose a Neural Inductive Matrix completion-based method with Graph Autoencoders (GAE) and Self-Attention mechanism for miRNA-disease associations prediction (NIMGSA). Some of the previous works based on matrix completion ignore the importance of label propagation procedure for inferring miRNA-disease associations, while others cannot integrate matrix completion and label propagation effectively. Varying from previous studies, NIMGSA unifies inductive matrix completion and label propagation via neural network architecture, through the collaborative training of two graph autoencoders. This neural inductive matrix completion-based method is also an implementation of self-attention mechanism for miRNA-disease associations prediction. This end-to-end framework can strengthen the robustness and preciseness of both matrix completion and label propagation. Cross validations indicate that NIMGSA outperforms current miRNA-disease prediction methods. Case studies demonstrate that NIMGSA is competent in detecting potential miRNA-disease associations.
| S-EPMC8774034 | biostudies-literature
Project description:Because of the catastrophic outbreak of global coronavirus disease 2019 (COVID-19) and its strong infectivity and possible persistence, computational repurposing of existing approved drugs will be a promising strategy that facilitates rapid clinical treatment decisions and provides reasonable justification for subsequent clinical trials and regulatory reviews. Since the effects of a small number of conditionally marketed vaccines need further clinical observation, there is still an urgent need to quickly and effectively repurpose potentially available drugs before the next disease peak. In this work, we have manually collected a set of experimentally confirmed virus-drug associations through the publicly published database and literature, consisting of 175 drugs and 95 viruses, as well as 933 virus-drug associations. Then, because the samples are extremely sparse and unbalanced, negative samples cannot be easily obtained. We have developed an ensemble model, EMC-Voting, based on matrix completion and weighted soft voting, a semi-supervised machine learning model for computational drug repurposing. Finally, we have evaluated the prediction performance of EMC-Voting by fivefold crossing-validation and compared it with other baseline classifiers and prediction models. The case study for the virus SARS-COV-2 included in the dataset demonstrates that our model achieves the outperforming AUPR value of 0.934 in virus-drug association's prediction.
| S-EPMC8334363 | biostudies-literature
Project description:BackgroundPhosphorylation events direct the flow of signals and metabolites along cellular protein networks. Current annotations of kinase-substrate binding events are far from complete. In this study, we scanned the entire human protein sequences using the PROSITE domain annotation tool to identify patterns of domain composition in kinases and their substrates. We identified statistically enriched pairs of strings of domains (signature pairs) in kinase-substrate couples presented in the 2006 version of the PTM database.ResultsThe signature pairs enriched in kinase - substrate binding interactions turned out to be highly specific to kinase subtypes. The resulting list of signature pairs predicted kinase-substrate interactions in validation dataset not used in learning with high statistical accuracy.ConclusionsThe method presented here produces predictions of protein phosphorylation events with high accuracy and mid-level coverage. Our method can be used in expanding the currently available drafts of cell signaling pathways and thus will be an important tool in the development of combination drug therapies targeting complex diseases.
| S-EPMC2912303 | biostudies-literature
Project description:BackgroundCurrently, numerous studies indicate that circular RNA (circRNA) is associated with various human complex diseases. While identifying disease-related circRNAs in vivo is time- and labor-consuming, a feasible and effective computational method to predict circRNA-disease associations is worthy of more studies.ResultsHere, we present a new method called SIMCCDA (Speedup Inductive Matrix Completion for CircRNA-Disease Associations prediction) to predict circRNA-disease associations. Based on known circRNA-disease associations, circRNA sequence similarity, disease semantic similarity, and the computed Gaussian interaction profile kernel similarity, we used speedup inductive matrix completion to construct the model. The proposed SIMCCDA method obtains an area under ROC curve (AUC) of 0.8465 with leave-one-out cross validation in the dataset, which is obtained by the combination of the three databases (circRNA disease, circ2Disease and circR2Disease). Our method surpasses other state-of-art models in predicting circRNA-disease associations. Furthermore, we conducted case studies in breast cancer, stomach cancer and colorectal cancer for further performance evaluation.ConclusionAll the results show reliable prediction ability of SIMCCDA. We anticipate that SIMCCDA could be utilized to facilitate further developments in the field and follow-up investigations by biomedical researchers.
| S-EPMC7118830 | biostudies-literature
Project description:Quantitative analysis of known drug-target interactions emerged in recent years as a useful approach for drug repurposing and assessing side effects. In the present study, we present a method that uses probabilistic matrix factorization (PMF) for this purpose, which is particularly useful for analyzing large interaction networks. DrugBank drugs clustered based on PMF latent variables show phenotypic similarity even in the absence of 3D shape similarity. Benchmarking computations show that the method outperforms those recently introduced provided that the input data set of known interactions is sufficiently large--which is the case for enzymes and ion channels, but not for G-protein coupled receptors (GPCRs) and nuclear receptors. Runs performed on DrugBank after hiding 70% of known interactions show that, on average, 88 of the top 100 predictions hit the hidden interactions. De novo predictions permit us to identify new potential interactions. Drug-target pairs implicated in neurobiological disorders are overrepresented among de novo predictions.
| S-EPMC3871285 | biostudies-literature