Functional Similarity Network Research Articles

SCPLPA: An miRNA-disease association prediction model based on spatial consistency projection and label propagation algorithm.

Identifying the association between miRNA and diseases is helpful for disease prevention, diagnosis and treatment. It is of great significance to use computational methods to predict potential human miRNA disease associations. Considering the shortcomings of existing computational methods, such as low prediction accuracy and weak generalization, we propose a new method called SCPLPA to predict miRNA-disease associations. First, a heterogeneous disease similarity network was constructed using the disease semantic similarity network and the disease Gaussian interaction spectrum kernel similarity network, while a heterogeneous miRNA similarity network was constructed using the miRNA functional similarity network and the miRNA Gaussian interaction spectrum kernel similarity network. Then, the estimated miRNA-disease association scores were evaluated by integrating the outcomes obtained by implementing label propagation algorithms in the heterogeneous disease similarity network and the heterogeneous miRNA similarity network. Finally, the spatial consistency projection algorithm of the network was used to extract miRNA disease association features to predict unverified associations between miRNA and diseases. SCPLPA was compared with four classical methods (MDHGI, NSEMDA, RFMDA and SNMFMDA), and the results of multiple evaluation metrics showed that SCPLPA exhibited the most outstanding predictive performance. Case studies have shown that SCPLPA can effectively identify miRNAs associated with colon neoplasms and kidney neoplasms. In summary, our proposed SCPLPA algorithm is easy to implement and can effectively predict miRNA disease associations, making it a reliable auxiliary tool for biomedical research.

Identifying the potential miRNA biomarkers based on multi-view networks and reinforcement learning for diseases.

MicroRNAs (miRNAs) play important roles in the occurrence and development of diseases. However, it is still challenging to identify the effective miRNA biomarkers for improving the disease diagnosis and prognosis. In this study, we proposed the miRNA data analysis method based on multi-view miRNA networks and reinforcement learning, miRMarker, to define the potential miRNA disease biomarkers. miRMarker constructs the cooperative regulation network and functional similarity network based on the expression data and known miRNA-disease relations, respectively. The cooperative regulation of miRNAs was evaluated by measuring the changes of relative expression. Natural language processing was introduced for calculating the miRNA functional similarity. Then, miRMarker integrates the multi-view miRNA networks and defines the informative miRNA modules through a reinforcement learning strategy. We compared miRMarker with eight efficient data analysis methods on nine transcriptomics datasets to show its superiority in disease sample discrimination. The comparison results suggested that miRMarker outperformed other data analysis methods in receiver operating characteristic analysis. Furthermore, the defined miRNA modules of miRMarker on colorectal cancer data not only show the excellent performance of cancer sample discrimination but also play significant roles in the cancer-related pathway disturbances. The experimental results indicate that miRMarker can build the robust miRNA interaction network by integrating the multi-view networks. Besides, exploring the miRNA interaction network using reinforcement learning favors defining the important miRNA modules. In summary, miRMarker can be a hopeful tool in biomarker identification for human diseases.

ILncDA-RSN: identification of lncRNA-disease associations based on reliable similarity networks.

Identification of disease-associated long non-coding RNAs (lncRNAs) is crucial for unveiling the underlying genetic mechanisms of complex diseases. Multiple types of similarity networks of lncRNAs (or diseases) can complementary and comprehensively characterize their similarities. Hence, in this study, we presented a computational model iLncDA-RSN based on reliable similarity networks for identifying potential lncRNA-disease associations (LDAs). Specifically, for constructing reliable similarity networks of lncRNAs and diseases, miRNA heuristic information with lncRNAs and diseases is firstly introduced to construct their respective Jaccard similarity networks; then Gaussian interaction profile (GIP) kernel similarity networks and Jaccard similarity networks of lncRNAs and diseases are provided based on the lncRNA-disease association network; a random walk with restart strategy is finally applied on Jaccard similarity networks, GIP kernel similarity networks, as well as lncRNA functional similarity network and disease semantic similarity network to construct reliable similarity networks. Depending on the lncRNA-disease association network and the reliable similarity networks, feature vectors of lncRNA-disease pairs are integrated from lncRNA and disease perspectives respectively, and then dimensionality reduced by the elastic net. Two random forests are at last used together on different lncRNA-disease association feature sets to identify potential LDAs. The iLncDA-RSN is evaluated by five-fold cross-validation to analyse its prediction performance, results of which show that the iLncDA-RSN outperforms the compared models. Furthermore, case studies of different complex diseases demonstrate the effectiveness of the iLncDA-RSN in identifying potential LDAs.

DAmiRLocGNet: miRNA subcellular localization prediction by combining miRNA-disease associations and graph convolutional networks.

MicroRNAs (miRNAs) are human post-transcriptional regulators in humans, which are involved in regulating various physiological processes by regulating the gene expression. The subcellular localization of miRNAs plays a crucial role in the discovery of their biological functions. Although several computational methods based on miRNA functional similarity networks have been presented to identify the subcellular localization of miRNAs, it remains difficult for these approaches to effectively extract well-referenced miRNA functional representations due to insufficient miRNA-disease association representation and disease semantic representation. Currently, there has been a significant amount of research on miRNA-disease associations, making it possible to address the issue of insufficient miRNA functional representation. In this work, a novel model is established, named DAmiRLocGNet, based on graph convolutional network (GCN) and autoencoder (AE) for identifying the subcellular localizations of miRNA. The DAmiRLocGNet constructs the features based on miRNA sequence information, miRNA-disease association information and disease semantic information. GCN is utilized to gather the information of neighboring nodes and capture the implicit information of network structures from miRNA-disease association information and disease semantic information. AE is employed to capture sequence semantics from sequence similarity networks. The evaluation demonstrates that the performance of DAmiRLocGNet is superior to other competing computational approaches, benefiting from implicit features captured by using GCNs. The DAmiRLocGNet has the potential to be applied to the identification of subcellular localization of other non-coding RNAs. Moreover, it can facilitate further investigation into the functional mechanisms underlying miRNA localization. The source code and datasets are accessed at http://bliulab.net/DAmiRLocGNet.

An urban crowd flow model integrating geographic characteristics

Predicting urban crowd flow spatial distributions plays a critical role in optimizing urban public safety and traffic congestion management. The spatial dependency between regions and the temporal dynamics of the local crowd flow are two important features in urban crowd flow prediction. However, few studies considered geographic characteristic in terms of spatial features. To fill this gap, we propose an urban crowd flow prediction model integrating geographic characteristics (FPM-geo). First, three geographic characteristics, proximity, functional similarity, and road network connectivity, are fused by a residual multigraph convolution network to model the spatial dependency relationship. Then, a long short-term memory network is applied as a framework to integrate both the temporal dynamic patterns of local crowd flow and the spatial dependency between regions. A 4-day mobile phone dataset validates the effectiveness of the proposed method by comparing it with several widely used approaches. The result shows that the root mean square error decreases by 15.37% compared with those of the typical models with the prediction interval at the 15-min level. The prediction error increases with the crowd flow size in a local area. Moreover, the error reaches the top of the morning peak and the evening peak and slopes down to the bottom at night.

DrugSim2DR: systematic prediction of drug functional similarities in the context of specific disease for drug repurposing.

Traditional approaches to drug development are costly and involve high risks. The drug repurposing approach can be a valuable alternative to traditional approaches and has therefore received considerable attention in recent years. Herein, we develop a previously undescribed computational approach, called DrugSim2DR, which uses a network diffusion algorithm to identify candidate anticancer drugs based on a drug functional similarity network. The innovation of the approach lies in the drug-drug functional similarity network constructed in a manner that implicitly links drugs through their common biological functions in the context of a specific disease state, as the similarity relationships based on general states (e.g., network proximity or Jaccard index of drug targets) ignore disease-specific molecular characteristics. The drug functional similarity network may provide a reference for prediction of drug combinations. We describe and validate the DrugSim2DR approach through analysis of data on breast cancer and lung cancer. DrugSim2DR identified some US Food and Drug Administration-approved anticancer drugs, as well as some candidate drugs validated by previous studies in the literature. Moreover, DrugSim2DR showed excellent predictive performance, as evidenced by receiver operating characteristic analysis and multiapproach comparisons in various cancer datasets. DrugSim2DR could accurately assess drug-drug functional similarity within a specific disease context and may more effectively prioritize disease candidate drugs. To increase the usability of our approach, we have developed an R-based software package, DrugSim2DR, which is freely available on CRAN (https://CRAN.R-project.org/package=DrugSim2DR).

Cortical gradient of a human functional similarity network captured by the geometry of cytoarchitectonic organization

Mapping the functional topology from a multifaceted perspective and relating it to underlying cross-scale structural principles is crucial for understanding the structural-functional relationships of the cerebral cortex. Previous works have described a sensory-association gradient axis in terms of coupling relationships between structure and function, but largely based on single specific feature, and the mesoscopic underpinnings are rarely determined. Here we show a gradient pattern encoded in a functional similarity network based on data from Human Connectome Project and further link it to cytoarchitectonic organizing principles. The spatial distribution of the primary gradient follows an inferior-anterior to superior-posterior axis. The primary gradient demonstrates converging relationships with layer-specific microscopic gene expression and mesoscopic cortical layer thickness, and is captured by the geometric representation of a myelo- and cyto-architecture based laminar differentiation theorem, involving a dual origin theory. Together, these findings provide a gradient, which describes the functional topology, and more importantly, linking the macroscale functional landscape with mesoscale laminar differentiation principles.

INTS-MFS: A novel method to predict microRNA-disease associations by integrating network topology similarity and microRNA function similarity

Identifying associations between microRNAs (miRNAs) and diseases is very important to understand the occurrence and development of human diseases. However, these existing methods suffer from the following limitation: first, some disease-related miRNAs are obtained from the miRNA functional similarity networks consisting of heterogeneous data sources, i.e., disease similarity, protein interaction network, gene expression. Second, little approaches infer disease-related miRNAs depending on the network topological features without the functional similarity of miRNAs. In this paper, we develop a novel model of Integrating Network Topology Similarity and MicroRNA Function Similarity (INTS-MFS). The integrated miRNA similarities are calculated based on miRNA functional similarity and network topological characteristics. INTS-MFS obtained AUC of 0.872 based on five-fold cross-validation and was applied to three common human diseases in case studies. As a results, 30 out of top 30 predicted Prostatic Neoplasm-related miRNAs were included in the two databases of dbDEMC and PhenomiR2.0. 29 out of top 30 predicted Lung Neoplasm-related miRNAs and Breast Neoplasm-related miRNAs were included in dbDEMC, PhenomiR2.0 and experimental reports. Moreover, INTS-MFS found unknown association with hsa-mir-371a in breast cancer and lung cancer, which have not been reported. It provides biologists new clues for diagnosing breast and lung cancer.

MSCFS: inferring circRNA functional similarity based on multiple data sources

BackgroundMore and more evidence shows that circRNA plays an important role in various biological processes and human health. Therefore, inferring the circRNA’s potential functions and obtaining circRNA functional similarity has become more and more significant. However, there is no effective approach to explore the functional similarity of circRNAs.MethodsIn this paper, we propose a new approach, called MSCFS, to calculate the functional similarity of circRNA by integrating multiple data sources. We combine circRNA-disease association, circRNA-gene-Gene Ontology association, and circRNA sequence information to explore the functional similarity of circRNA. Firstly, we employ different learning representation methods from three data sources to establish three circRNA functional similarity networks. Then we integrate the three networks to obtain the final circRNA functional similarity.ResultsWe utilize circRNA–miRNA association similarity and circRNA co-expression similarity to evaluate the performance of MSCFS. The results show a positive correlation with miRNA association (R=0.213) and circRNA co-expression similarity (R=0.8991). Finally, we construct a circRNA functional similarity network and perform case analysis. The result shows our method can be applied to infer new potential functions of circRNA and other associations.ConclusionsMSCFS combines multiple data sources related to circRNA functions. Correlation analysis and case analyses prove that MSCFS is a useful method to explore circRNA functional similarity.

Similarity Calculation, Enrichment Analysis, and Ontology Visualization of Biomedical Ontologies using UFO.

The rapid growth of biomedical ontologies observed in recent years has been reported to be useful in various applications. In this article, we propose two main-function protocols-term-related and entity-related-with the three most common ontology analyses, including similarity calculation, enrichment analysis, and ontology visualization, which can be done by separate methods. Many previously developed tools implementing those methods run on different platforms and implement a limited number of the methods for similarity calculation and enrichment analysis tools for a specific type of biomedical ontology, although any type can be acceptable. Moreover, depending on each application, methods have distinct advantages; thus, the greater the number of methods a tool has, the better decisions that users make. The protocol here implements all the analyses above using an advanced popular tool called UFO. UFO is a Cytoscape app that unifies most of the semantic similarity measures for between-term and between-entity similarity calculation for biomedical ontologies in OBO format, which can calculate the similarity between two sets of entities and weigh imported entity networks, as well as generate functional similarity networks. The complete protocol can be performed in 30 min and is designed for use by biologists with no prior bioinformatics training. © 2021 Wiley Periodicals LLC. Basic Protocol: Running UFO using a list of input Gene Ontology, Disease Ontology, or Human Phenotype Ontology data.

Logistic Weighted Profile-Based Bi-Random Walk for Exploring MiRNA-Disease Associations

MicroRNAs (miRNAs) exert an enormous influence on cell differentiation, biological development and the onset of diseases. Because predicting potential miRNA-disease associations (MDAs) by biological experiments usually requires considerable time and money, a growing number of researchers are working on developing computational methods to predict MDAs. High accuracy is critical for prediction. To date, many algorithms have been proposed to infer novel MDAs. However, they may still have some drawbacks. In this paper, a logistic weighted profile-based bi-random walk method (LWBRW) is designed to infer potential MDAs based on known MDAs. In this method, three networks (i.e., a miRNA functional similarity network, a disease semantic similarity network and a known MDA network) are constructed first. In the process of building the miRNA network and the disease network, Gaussian interaction profile (GIP) kernel is computed to increase the kernel similarities, and the logistic function is used to extract valuable information and protect known MDAs. Next, the known MDA matrix is preprocessed by the weighted K-nearest known neighbours (WKNKN) method to reduce the number of false negatives. Then, the LWBRW method is applied to infer novel MDAs by bi-randomly walking on the miRNA network and the disease network. Finally, the predictive ability of the LWBRW method is confirmed by the average AUC of 0.939 3 (0.006 1) in 5-fold cross-validation (CV) and the AUC value of 0.976 3 in leave-one-out cross-validation (LOOCV). In addition, case studies also show the outstanding ability of the LWBRW method to explore potential MDAs.

Exploring miRNA Sponge Networks of Breast Cancer by Combining miRNA-disease-lncRNA and miRNA-target Networks

Background: Recently, ample researches show that microRNAs (miRNAs) not only interact with coding genes but interact with a pool of different RNAs. Those RNAs are called miRNA sponges, including long non-coding RNAs (lncRNAs), circular RNA, pseudogenes and various messenger RNAs. Understanding regulatory networks of miRNA sponges can better help researchers to study the mechanisms of breast cancers. Objective: We develop a new method to explore miRNA sponge networks of breast cancer by combining miRNAdisease-lncRNA and miRNA-target networks (MSNMDL). Method: Firstly, MSNMDL infers miRNA-lncRNA functional similarity networks from miRNAdisease- lncRNA networks. Secondly, MSNMDL forms lncRNA-target networks by using lncRNA to replace the role of matched miRNA in miRNA-target networks according to the lncRNA-miRNA pair of miRNA-lncRNA functional similarity networks. And MSNMDL only retains the genes of breast cancer in lncRNA-target networks to construct candidate miRNA sponge networks. Thirdly, MSNMDL merges these candidate miRNA sponge networks with other miRNA sponge interactions and then selects top-hub lncRNA and its interactions to construct miRNA sponge networks. Results: MSNMDL is superior to other methods in terms of biological significance and its identified modules might act as module signatures for prognostication of breast cancer. Conclusion: MiRNA sponge networks identified by MSNMDL are biologically significant and are closely associated with breast cancer, which makes MSNMDL a promising way for researchers to study the pathogenesis of breast cancer.

CircRNA-disease associations prediction based on metapath2vec++ and matrix factorization

Circular RNA (circRNA) is a novel non-coding endogenous RNAs. Evidence has shown that circRNAs are related to many biological processes and play essential roles in different biological functions. Although increasing numbers of circRNAs are discovered using high-throughput sequencing technologies, these techniques are still time-consuming and costly. In this study, we propose a computational method to predict circRNA-disesae associations which is based on metapath2vec++ and matrix factorization with integrated multiple data (called PCD MVMF). To construct more reliable networks, various aspects are considered. Firstly, circRNA annotation, sequence, and functional similarity networks are established, and disease-related genes and semantics are adopted to construct disease functional and semantic similarity networks. Secondly, metapath2vec++ is applied on an integrated heterogeneous network to learn the embedded features and initial prediction score. Finally, we use matrix factorization, take similarity as a constraint, and optimize it to obtain the final prediction results. Leave-one-out cross-validation, five-fold cross-validation, and f-measure are adopted to evaluate the performance of PCD MVMF. These evaluation metrics verify that PCD MVMF has better prediction performance than other methods. To further illustrate the performance of PCD MVMF, case studies of common diseases are conducted. Therefore, PCD MVMF can be regarded as a reliable and useful circRNA-disease association prediction tool.

Scalable Non-Linear Graph Fusion for Prioritizing Cancer-Causing Genes.

In the past few decades, both gene expression data and protein-protein interaction (PPI)networks have been extensively studied, due to their ability to depict important characteristics of disease-associated genes. In this regard, the paper presents a new gene prioritization algorithm to identify and prioritize cancer-causing genes, integrating judiciously the complementary information obtained from two data sources. The proposed algorithm selects disease-causing genes by maximizing the importance of selected genes and functional similarity among them. A new quantitative index is introduced to evaluate the importance of a gene. It considers whether a gene exhibits a differential expression pattern across sick and healthy individuals, and has a strong connectivity in the PPI network, which are the important characteristics of a potential biomarker. As disease-associated genes are expected to have similar expression profiles and topological structures, a scalable non-linear graph fusion technique, termed as ScaNGraF, is proposed to learn a disease-dependent functional similarity network from the co-expression and common neighbor based similarity networks. The proposed ScaNGraF, which is based on message passing algorithm, efficiently combines the shared and complementary information provided by different data sources with significantly lower computational cost. A new measure, termed as DiCoIN, is introduced to evaluate the quality of a learned affinity network. The performance of the proposed graph fusion technique and gene selection algorithm is extensively compared with that of some existing methods, using several cancer data sets.

ES-MDA: Enhanced Similarity-based MiRNA-Disease Association.

Accumulating evidence demonstrate that miRNAs can be treated as critical biomarkers in various complex human diseases. Thus, the identifications on potential miRNA-disease associations have become a hotpot for providing better understanding of disease pathology in this field. Recently, with various biological datasets, increasingly computational prediction approaches have been designed to uncover disease-related miRNAs for further experimental validation. To improve the prediction accuracy, several algorithms integrated miRNA similarities of known miRNA-disease associations to enhance the miRNA functional similarity network and disease similarities of known miRNA-disease associations to enhance the disease semantic similarity network. It is anticipated that machine learning methods would become an effective biological resource for clinical experimental guidance.

UFO: A tool for unifying biomedical ontology-based semantic similarity calculation, enrichment analysis and visualization.

BackgroundBiomedical ontologies have been growing quickly and proven to be useful in many biomedical applications. Important applications of those data include estimating the functional similarity between ontology terms and between annotated biomedical entities, analyzing enrichment for a set of biomedical entities. Many semantic similarity calculation and enrichment analysis methods have been proposed for such applications. Also, a number of tools implementing the methods have been developed on different platforms. However, these tools have implemented a small number of the semantic similarity calculation and enrichment analysis methods for a certain type of biomedical ontology. Note that the methods can be applied to all types of biomedical ontologies. More importantly, each method can be dominant in different applications; thus, users have more choice with more number of methods implemented in tools. Also, more functions would facilitate their task with ontology.ResultsIn this study, we developed a Cytoscape app, named UFO, which unifies most of the semantic similarity measures for between-term and between-entity similarity calculation for all types of biomedical ontologies in OBO format. Based on the similarity calculation, UFO can calculate the similarity between two sets of entities and weigh imported entity networks as well as generate functional similarity networks. Besides, it can perform enrichment analysis of a set of entities by different methods. Moreover, UFO can visualize structural relationships between ontology terms, annotating relationships between entities and terms, and functional similarity between entities. Finally, we demonstrated the ability of UFO through some case studies on finding the best semantic similarity measures for assessing the similarity between human disease phenotypes, constructing biomedical entity functional similarity networks for predicting disease-associated biomarkers, and performing enrichment analysis on a set of similar phenotypes.ConclusionsTaken together, UFO is expected to be a tool where biomedical ontologies can be exploited for various biomedical applications.AvailabilityUFO is distributed as a Cytoscape app, and can be downloaded freely at Cytoscape App (http://apps.cytoscape.org/apps/ufo) for non-commercial use

Inferring MicroRNA-Disease Associations Based on the Identification of a Functional Module.

Inferring potential associations between microRNAs (miRNAs) and human diseases can help people understand the pathogenesis of complex human diseases. Several computational approaches have been presented to discover novel miRNA-disease associations based on a top-ranked association model. However, some top-ranked miRNAs are not easily used to reveal the association between miRNAs and diseases. This study aims to infer miRNA-disease relationship by identifying a functional module. We first construct a miRNA functional similarity network derived from a disease similarity network and a known miRNA-disease relationship network. We then present an improved K-means (i.e., IK-means) algorithm to detect miRNA functional modules and used 243 diseases to validate the performance of our proposed method. Experimental results indicate that the performance of IK-means is better compared with classical K-means algorithms. Case studies on some functional modules further demonstrate the applicability of IK-means in the identification of new miRNA-disease associations.

Inferring lncRNA Functional Similarity Based on Integrating Heterogeneous Network Data

Although lncRNAs lack the potential to be translated into proteins directly, their complicated and diversiform functions make them as a window into decoding the mechanisms of human physiological activities. Accumulating experiment studies have identified associations between lncRNA dysfunction and many important complex diseases. However, known experimentally confirmed lncRNA functions are still very limited. It is urgent to build effective computational models for rapid predicting of unknown lncRNA functions on a large scale. To this end, valid similarity measure between known and unknown lncRNAs plays a vital role. In this paper, an original model was developed to calculate functional similarities between lncRNAs by integrating heterogeneous network data. In this model, a novel integrated network was constructed based on the data of four single lncRNA functional similarity networks (miRNA-based similarity network, disease-based similarity network, GTEx expression-based network and NONCODE expression-based network). Using the lncRNA pairs that share the target mRNAs as the benchmark, the results show that this integrated network is more effective than any single networks with an AUC of 0.736 in the cross validation, while the AUC of four single networks were 0.703, 0.733, 0.611, and 0.602. To implement our model, a web server named IHNLncSim was constructed for inferring lncRNA functional similarity based on integrating heterogeneous network data. Moreover, the modules of network visualization and disease-based lncRNA function enrichment analysis were added into IHNLncSim. It is anticipated that IHNLncSim could be an effective bioinformatics tool for the researches of lncRNA regulation function studies. IHNLncSim is freely available at http://www.lirmed.com/ihnlncsim.

Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profile in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies. The incidence of MDS is gradually increasing, but the pathogenesis is still not very clear. Studies have shown that long non-coding RNAs (lncRNAs) play a critical role in both oncogenic and tumor-suppressive pathways. However, the function of lncRNAs in MDS is still unknown. The purpose of this study was to investigate the expression profiles and biological function of the aberrantly expressed lncRNAs and mRNAs in MDS. We downloaded two data sets (GSE4619 and GSE19429) from the Gene Expression Omnibus database and obtained differentially expressed (DE) lncRNAs and DE-mRNAs between MDS cases and healthy controls. Then we performed systematic bioinformatics analysis to know the biological function of DE-lncRNAs and DE-mRNAs in MDS. We identified 40 DE-lncRNAs and 643 DE-mRNAs between MDS cases and healthy controls. Gene Ontology (GO) and pathway analysis revealed that DE-lncRNAs and DE-mRNAs were mainly involved in necroptosis, apoptosis, immunodeficiency, p53 and FoxO signaling pathways. LncRNA-mRNA co-expression and lncRNA functional similarity network showed that twelve down-regulated lncRNAs co-regulated the same target gene and they were similar in function. The comprehensive analysis of lncRNA and mRNA is helpful in understanding the pathogenesis of MDS, and the synergistically down-regulated lncRNAs may contribute to the development of new diagnostic and therapeutic strategies.

Learning Multimodal Networks From Heterogeneous Data for Prediction of lncRNA-miRNA Interactions.

Long noncoding RNAs (lncRNAs) is an important class of non-protein coding RNAs. They have recently been found to potentially be able to act as a regulatory molecule in some important biological processes. MicroRNAs (miRNAs) have been confirmed to be closely related to the regulation of various human diseases. Recent studies have suggested that lncRNAs could interact with miRNAs to modulate their regulatory roles. Hence, predicting lncRNA-miRNA interactions are biologically significant due to their potential roles in determining the effectiveness of diagnostic biomarkers and therapeutic targets for various human diseases. For the details of the mechanisms to be better understood, it would be useful if some computational approaches are developed to allow for such investigations. As diverse heterogeneous datasets for describing lncRNA and miRNA have been made available, it becomes more feasible for us to develop a model to describe potential interactions between lncRNAs and miRNAs. In this work, we present a novel computational approach called LMNLMI for such purpose. LMNLMI works in several phases. First, it learns patterns from expression, sequences and functional data. Based on the patterns, it then constructs several networks including an expression-similarity network, a functional-similarity network, and a sequence-similarity network. Based on a measure of similarities between these networks, LMNLMI computes an interaction score for each pair of lncRNA and miRNA in the database. The novelty of LMNLMI lies in the use of a network fusion technique to combine the patterns inherent in multiple similarity networks and a matrix completion technique in predicting interaction relationships. Using a set of real data, we show that LMNLMI can be a very effective approach for the accurate prediction of lncRNA-miRNA interactions.