Prediction of lncRNA-disease association based on a Laplace normalized random walk with restart algorithm on heterogeneous networks

Background More and more evidence showed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human sophisticated diseases. Therefore, predicting human lncRNA-disease associations is a challenging and urgently task in bioinformatics to research of human sophisticated diseases. Results In the work, a global network-based computational framework called as LRWRHLDA were proposed which is a universal network-based method. Firstly, four isomorphic networks include lncRNA similarity network, disease similarity network, gene similarity network and miRNA similarity network were constructed. And then, six heterogeneous networks include known lncRNA-disease, lncRNA-gene, lncRNA-miRNA, disease-gene, disease-miRNA, and gene-miRNA associations network were applied to design a multi-layer network. Finally, the Laplace normalized random walk with restart algorithm in this global network is suggested to predict the relationship between lncRNAs and diseases. Conclusions The ten-fold cross validation is used to evaluate the performance of LRWRHLDA. As a result, LRWRHLDA achieves an AUC of 0.98402, which is higher than other compared methods. Furthermore, LRWRHLDA can predict isolated disease-related lnRNA (isolated lnRNA related disease). The results for colorectal cancer, lung adenocarcinoma, stomach cancer and breast cancer have been verified by other researches. The case studies indicated that our method is effective.

A Random Walk with Restart Model Based on Common Neighbors for Predicting the Clinical Drug Combinations on Coronary Heart Disease

As the approaching of the clinical big data era, the prediction of whether drugs can be used in combination in clinical practice is a fundamental problem in the analysis of medical data. Compared with high-throughput screening, it is more cost-effective to treat this problem as a link prediction problem and predict by algorithms. Inspired by the rule of combined clinical medication, a new computational model is proposed. The drug-drug combination was predicted by combining the number of adjacent complete subgraphs shared by the two points with the restart random walk algorithm. The model is based on the semisupervised random walk algorithm, and the same neighborhood is used to improve the random walk with restart (CN-RWR). The algorithm can effectively improve the prediction performance and assign a score to any combination of drugs. To fairly compare the predictive performance of the improved model with that of the random walk with restart model (RWR), a cross-validation of the two models on the same drug data was performed. The AUROC of CN-RWR and RWR under the LOOCV validation framework is 0.9741 and 0.9586, respectively, and the improved model results are more reliable. In addition, the top 3 predictive drug combinations have been approved by the public. The new model is expected that this model can be extended to predict the use of combination drugs for other diseases to find combinations of drugs with potential clinical benefits.

A network-based method for predicting disease-associated enhancers

Background Enhancers regulate transcription of target genes, causing a change in expression level. Thus, the aberrant activity of enhancers can lead to diseases. To date, a large number of enhancers have been identified, yet a small portion of them have been found to be associated with diseases. This raises a pressing need to develop computational methods to predict associations between diseases and enhancers. Results In this study, we assumed that enhancers sharing target genes could be associated with similar diseases to predict the association. Thus, we built an enhancer functional interaction network by connecting enhancers significantly sharing target genes, then developed a network diffusion method RWDisEnh, based on a random walk with restart algorithm, on networks of diseases and enhancers to globally measure the degree of the association between diseases and enhancers. RWDisEnh performed best when the disease similarities are integrated with the enhancer functional interaction network by known disease-enhancer associations in the form of a heterogeneous network of diseases and enhancers. It was also superior to another network diffusion method, i.e., PageRank with Priors, and a neighborhood-based one, i.e., MaxLink, which simply chooses the closest neighbors of known disease-associated enhancers. Finally, we showed that RWDisEnh could predict novel enhancers, which are either directly or indirectly associated with diseases. Conclusions Taken together, RWDisEnh could be a potential method for predicting disease-enhancer associations.

Use of a Network-Based Method to Identify Latent Genes Associated with Hearing Loss in Children

Hearing loss is a total or partial inability to hear. Approximately 5% of people worldwide experience this condition. Hearing capacity is closely related to language, social, and basic emotional development; hearing loss is particularly serious in children. The pathogenesis of childhood hearing loss remains poorly understood. Here, we sought to identify new genes potentially associated with two types of hearing loss in children: congenital deafness and otitis media. We used a network-based method incorporating a random walk with restart algorithm, as well as a protein-protein interaction framework, to identify genes potentially associated with either pathogenesis. A following screening procedure was performed and 18 and 87 genes were identified, which potentially involved in the development of congenital deafness or otitis media, respectively. These findings provide novel biomarkers for clinical screening of childhood deafness; they contribute to a genetic understanding of the pathogenetic mechanisms involved.

A Random Walk-Based Method to Identify Candidate Genes Associated With Lymphoma

Lymphoma is a serious type of cancer, especially for adolescents and elder adults, although this malignancy is quite rare compared with other types of cancer. The cause of this malignancy remains ambiguous. Genetic factor is deemed to be highly associated with the initiation and progression of lymphoma, and several genes have been related to this disease. Determining the pathogeny of lymphoma by identifying the related genes is important. In this study, we presented a random walk-based method to infer the novel lymphoma-associated genes. From the reported 1,458 lymphoma-associated genes and protein–protein interaction network, raw candidate genes were mined by using the random walk with restart algorithm. The determined raw genes were further filtered by using three screening tests (i.e., permutation, linkage, and enrichment tests). These tests could control false-positive genes and screen out essential candidate genes with strong linkages to validate the lymphoma-associated genes. A total of 108 inferred genes were obtained. Analytical results indicated that some inferred genes, such as RAC3, TEC, IRAK2/3/4, PRKCE, SMAD3, BLK, TXK, PRKCQ, were associated with the initiation and progression of lymphoma.

Predicting miRNA–disease associations using improved random walk with restart and integrating multiple similarities

Predicting beneficial and valuable miRNA–disease associations (MDAs) by doing biological laboratory experiments is costly and time-consuming. Proposing a forceful and meaningful computational method for predicting MDAs is essential and captivated many computer scientists in recent years. In this paper, we proposed a new computational method to predict miRNA–disease associations using improved random walk with restart and integrating multiple similarities (RWRMMDA). We used a WKNKN algorithm as a pre-processing step to solve the problem of sparsity and incompletion of data to reduce the negative impact of a large number of missing associations. Two heterogeneous networks in disease and miRNA spaces were built by integrating multiple similarity networks, respectively, and different walk probabilities could be designated to each linked neighbor node of the disease or miRNA node in line with its degree in respective networks. Finally, an improve extended random walk with restart algorithm based on miRNA similarity-based and disease similarity-based heterogeneous networks was used to calculate miRNA–disease association prediction probabilities. The experiments showed that our proposed method achieved a momentous performance with Global LOOCV AUC (Area Under Roc Curve) and AUPR (Area Under Precision-Recall Curve) values of 0.9882 and 0.9066, respectively. And the best AUC and AUPR values under fivefold cross-validation of 0.9855 and 0.8642 which are proven by statistical tests, respectively. In comparison with other previous related methods, it outperformed than NTSHMDA, PMFMDA, IMCMDA and MCLPMDA methods in both AUC and AUPR values. In case studies of Breast Neoplasms, Carcinoma Hepatocellular and Stomach Neoplasms diseases, it inferred 1, 12 and 7 new associations out of top 40 predicted associated miRNAs for each disease, respectively. All of these new inferred associations have been confirmed in different databases or literatures.

ImmunAL: a frame to identify the immunological markers for Mild Moderated Alzheimer's Disease applying Multiplex Network Model

Identification of immunological markers for neurodegenerative diseases resolve issues related to diagnostic and therapeutic. Neuro-specific cells experience disruptive mechanisms in the early stages of disease progression. The autophagy mechanism, guided by the autoantibodies, is one of the prime indicators of neurodegenerative diseases. Identifying autoantibodies can show a new direction. Detecting influential autoantibodies from relational networks viz., co-expression, co-methylation, etc. is a well-studied area. However, none of the studies have considered the functional affinity among the autoantibodies while selecting them from a relational network. In this regard, a two-layered multiplex network based framework has been proposed,whereby the layers consist co-expression and co-semantic scores. The networks have been formed using three distinct cases viz., diseased, controlled, and a combination of both. Subsequently, a random walk with restart mechanism has been applied to identify the influential autoantibodies, where layer switching probability and restart probability are 0.5 and 0.4 respectively. Next, pathway semantic network has been formed considering the autoantibody associated pathways. EPO and IL1RN, associated with a maximum number of pathways, are identified as the two most influential autoantibodies. The network also provides insights into possible molecular mechanisms during the pathogenic progression. Finally, MDPI and CNN3 are also identified as important biomarkers.

Predicting LncRNA–Disease Association by a Random Walk With Restart on Multiplex and Heterogeneous Networks

Studies have found that long non-coding RNAs (lncRNAs) play important roles in many human biological processes, and it is critical to explore potential lncRNA–disease associations, especially cancer-associated lncRNAs. However, traditional biological experiments are costly and time-consuming, so it is of great significance to develop effective computational models. We developed a random walk algorithm with restart on multiplex and heterogeneous networks of lncRNAs and diseases to predict lncRNA–disease associations (MHRWRLDA). First, multiple disease similarity networks are constructed by using different approaches to calculate similarity scores between diseases, and multiple lncRNA similarity networks are also constructed by using different approaches to calculate similarity scores between lncRNAs. Then, a multiplex and heterogeneous network was constructed by integrating multiple disease similarity networks and multiple lncRNA similarity networks with the lncRNA–disease associations, and a random walk with restart on the multiplex and heterogeneous network was performed to predict lncRNA–disease associations. The results of Leave-One-Out cross-validation (LOOCV) showed that the value of Area under the curve (AUC) was 0.68736, which was improved compared with the classical algorithm in recent years. Finally, we confirmed a few novel predicted lncRNAs associated with specific diseases like colon cancer by literature mining. In summary, MHRWRLDA contributes to predict lncRNA–disease associations.

Biased Random Walk With Restart on Multilayer Heterogeneous Networks for MiRNA–Disease Association Prediction

Numerous experiments have proved that microRNAs (miRNAs) could be used as diagnostic biomarkers for many complex diseases. Thus, it is conceivable that predicting the unobserved associations between miRNAs and diseases is extremely significant for the medical field. Here, based on heterogeneous networks built on the information of known miRNA–disease associations, miRNA function similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases, we developed a computing model of biased random walk with restart on multilayer heterogeneous networks for miRNA–disease association prediction (BRWRMHMDA) through enforcing degree-based biased random walk with restart (BRWR). Assessment results reflected that an AUC of 0.8310 was gained in local leave-one-out cross-validation (LOOCV), which proved the calculation algorithm’s good performance. Besides, we carried out BRWRMHMDA to prioritize candidate miRNAs for esophageal neoplasms based on HMDD v2.0. We further prioritize candidate miRNAs for breast neoplasms based on HMDD v1.0. The local LOOCV results and performance analysis of the case study all showed that the proposed model has good and stable performance.