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Circular RNAs (circRNAs) play a crucial role in gene regulation and association with diseases because of their unique closed continuous loop structure, which is more stable and conserved than ordinary linear RNAs. As fundamental work to clarify their functions, a large number of computational approaches for identifying circRNA formation have been proposed. However, these methods fail to fully utilize the important characteristics of back-splicing events, i.e., the positional information of the splice sites and the interaction features of its flanking sequences, for predicting circRNAs. To this end, we hereby propose a novel approach called SIDE for predicting circRNA back-splicing events using only raw RNA sequences. Technically, SIDE employs a dual encoder to capture global and interactive features of the RNA sequence, and then a decoder designed by the contrastive learning to fuse out discriminative features improving the prediction of circRNAs formation. Empirical results on three real-world datasets show the effectiveness of SIDE. Further analysis also reveals that the effectiveness of SIDE.

To identify similar diseases has significant implications for revealing the etiology and pathogenesis of diseases and further research in the domain of biomedicine. Currently, most methods for the measurement of disease similarity utilize either associations of ontological disease concepts or functional interactions between disease-related genes. These methods are heavily dependent on the ontology, which are not always available, and the selection of datasets. Moreover, many methods suffer from a drawback that they only use a single metric to evaluate disease similarity from an individual data source, which may result in biased conclusions without consideration of other aspects. In this study, we proposed a novel ontology-independent framework, namely RADAR, for learning representations for diseases to deduce their similarities from an integrative perspective. By leveraging the associations between diseases and disease-related biomedical entities, a disease similarity network was built under various metrics. Then, a multi-layer disease similarity network was constructed by integrating multiple disease similarity networks derived from multiple data sources, where the representation learning was derived to provide a comprehensive evaluation of disease similarities. The performance of RADAR was assessed by a benchmark disease set and 100 random disease sets. Experimental results demonstrated that RADAR can detect similar diseases effectively.

Background: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors and its average survival time is less than 1 year after diagnosis., Results: Firstly, this study aims to develop the novel survival analysis algorithms to explore the key genes and proteins related to GBM. Then, we explore the significant correlation between AEBP1 upregulation and increased EGFR expression in primary glioma, and employ a glioma cell line LN229 to identify relevant proteins and molecular pathways through protein network analysis. Finally, we identify that AEBP1 exerts its tumor-promoting effects by mainly activating mTOR pathway in Glioma., Conclusions: We summarize the whole process of the experiment and discuss how to expand our experiment in the future.

Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used.

Background: The identification of genes and uncovering the role they play in diseases is an important and complex challenge. Genome-wide linkage and association studies have made advancements in identifying genetic variants that underpin human disease. An important challenge now is to identify meaningful disease-associated genes from a long list of candidate genes implicated by these analyses. The application of gene prioritization can enhance our understanding of disease mechanisms and aid in the discovery of drug targets. The integration of protein-protein interaction networks along with disease datasets and contextual information is an important tool in unraveling the molecular basis of diseases., Results: In this paper we propose a computational pipeline for the prioritization of disease-gene candidates. Diverse heterogeneous data including: gene-expression, protein-protein interaction network, ontology-based similarity and topological measures and tissue-specific are integrated. The pipeline was applied to prioritize Alzheimer's Disease (AD) genes, whereby a list of 32 prioritized genes was generated. This approach correctly identified key AD susceptible genes: PSEN1 and TRAF1. Biological process enrichment analysis revealed the prioritized genes are modulated in AD pathogenesis including: regulation of neurogenesis and generation of neurons. Relatively high predictive performance (AUC: 0.70) was observed when classifying AD and normal gene expression profiles from individuals using leave-one-out cross validation., Conclusions: This work provides a foundation for future investigation of diverse heterogeneous data integration for disease-gene prioritization.

The organization of global protein interaction networks (PINs) has been extensively studied and heatedly debated. We revisited this issue in the context of the analysis of dynamic organization of a PIN in the yeast cell cycle. Statistically significant bimodality was observed when analyzing the distribution of the differences in expression peak between periodically expressed partners. A close look at their behavior revealed that date and party hubs derived from this analysis have some distinct features. There are no significant differences between them in terms of protein essentiality, expression correlation and semantic similarity derived from gene ontology (GO) biological process hierarchy. However, date hubs exhibit significantly greater values than party hubs in terms of semantic similarity derived from both GO molecular function and cellular component hierarchies. Relating to three-dimensional structures, we found that both single- and multi-interface proteins could become date hubs coordinating multiple functions performed at different times while party hubs are mainly multi-interface proteins. Furthermore, we constructed and analyzed a PPI network specific to the human cell cycle and highlighted that the dynamic organization in human interactome is far more complex than the dichotomy of hubs observed in the yeast cell cycle.

The idea of the existence of date and party hubs in protein-protein interaction networks has been debated since it was proposed in 2004. Based on the incorporation of the information extracted from known three-dimensional structures of protein interactions, we revisited the properties associated with date and party hubs previously identified. The correlation of genomic essentiality, gene coexpression, and functional semantic similarity with date and party hubs were examined. The number of interaction interfaces associated with each hub was taken into account. The results suggested that the identification of date and party hubs based on their network connectivity and expression profiles with interaction partners may be incomplete. The number of interaction interfaces could play an important role in examining functional and topological properties associated with each hub protein. The observation is robust to the choice of degree cutoffs for hubs. Furthermore, we found that while singlish-interface hubs seem to correspond mostly to date hub, it appears that there is no significant difference between the proportions of multi-interface proteins categorized as date and as party hubs.

The discovery of novel disease biomarkers is a crucial challenge for translational bioinformatics. Demonstration of both their classification power and reproducibility across independent datasets are essential requirements to assess their potential clinical relevance. Small datasets and multiplicity of putative biomarker sets may explain lack of predictive reproducibility. Studies based on pathway-driven discovery approaches have suggested that, despite such discrepancies, the resulting putative biomarkers tend to be implicated in common biological processes. Investigations of this problem have been mainly focused on datasets derived from cancer research. We investigated the predictive and functional concordance of five methods for discovering putative biomarkers in four independently-generated datasets from the cardiovascular disease domain. A diversity of biosignatures was identified by the different methods. However, we found strong biological process concordance between them, especially in the case of methods based on gene set analysis. With a few exceptions, we observed lack of classification reproducibility using independent datasets. Partial overlaps between our putative sets of biomarkers and the primary studies exist. Despite the observed limitations, pathway-driven or gene set analysis can predict potentially novel biomarkers and can jointly point to biomedically-relevant underlying molecular mechanisms., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In this paper, we propose a new random walk-based clustering algorithm for detecting functional modules in protein-protein interaction (PPI) networks. It has been tested on two yeast PPI networks. Greater precision, better homogeneity and higher modularity were achieved in comparison with the results produced by the recently developed RRW clustering technique and the well-known CFinder algorithm. A much higher level of true positives were observed in the clustering results. The analysis indicated that the proposed method can not only detect overlapping modules but also be potentially used to identify functional modules with different topological structures, which may not be highly connected.

Summary: A standard systems-based approach to biomarker and drug target discovery consists of placing putative biomarkers in the context of a network of biological interactions, followed by different 'guilt-by-association' analyses. The latter is typically done based on network structural features. Here, an alternative analysis approach in which the networks are analyzed on a 'semantic similarity' space is reported. Such information is extracted from ontology-based functional annotations. We present SimTrek, a Cytoscape plugin for ontology-based similarity assessment in biological networks., Availability: http://rosalind.infj.ulst.ac.uk/SimTrek.html, Contact: francisco.azuaje@crp-sante.lu, Supplementary Information: Supplementary data are available at Bioinformatics online.

A fully extended Protein Protein Interaction (PPI) network can consist of upwards of several thousand nodes and edges. To simplify analysis, smaller child samples are often used in substitution of the global network. In this study, the impact of different levels of sampling was evaluated on six PPI networks. Results from the case studies suggest that restricting analysis to the first network level, using metrics such as degree and BC, could lead to misrepresentative results, omitting potentially significant nodes. Fault-tolerance analysis also indicates that key nodes within the second network level, and above, contribute to the stability of the global network.

Keywords: omics; machine learning; drug; RNA; disease; biomarker; network analysis; deep learning EN omics machine learning drug RNA disease biomarker network analysis deep learning N.PAG N.PAG 4 12/29/20 20201223 NES 201223 Due to the high experimental cost and the exponential decline in the cost of high-throughput sequencing, computational models, and methods are preferred by scholars. In Li S. et al., on the strength of a matrix containing microbes similarity, disease similarity and a bipartite graph network of the two interactions, the potential microbe-disease associations are calculated by Katz centrality. Omics, machine learning, drug, RNA, disease, biomarker, network analysis, deep learning. [Extracted from the article]

In this study, a minimum dominating set based approach was developed and implemented as a Cytoscape plugin to identify critical and redundant proteins in a protein interaction network. We focused on the investigation of the properties associated with critical proteins in the context of the analysis of interaction networks specific to cell cycle in both yeast and human. A total of 132 yeast genes and 129 human proteins have been identified as critical nodes while 950 in yeast and 980 in human have been categorized as redundant nodes. A clear distinction between critical and redundant proteins was observed when examining their topological parameters including betweenness centrality, suggesting a central role of critical proteins in the control of a network. The significant differences in terms of gene coexpression and functional similarity were observed between the two sets of proteins in yeast. Critical proteins were found to be enriched with essential genes in both networks and have a more deleterious effect on the network integrity than their redundant counterparts. Furthermore, we obtained statistically significant enrichments of proteins that govern human diseases including cancer-related and virus-targeted genes in the corresponding set of critical proteins. [ABSTRACT FROM PUBLISHER]

Abstract: Modeling and simulation of gene-regulatory networks (GRNs) has become an important aspect of modern computational biology investigations into gene regulation. A key challenge in this area is the automated inference (reverse-engineering) of dynamic, mechanistic GRN models from time-course gene expression data. Common mathematical formalisms used to represent such models capture both the relative weight or strength of a regulator gene and the type of the regulator (activator, repressor) with a single model parameter. The goal of this study is to quantify the role this parameter plays in terms of the computational performance of the reverse-engineering process and the predictive power of the inferred GRN models. We carried out three sets of computational experiments on a GRN system consisting of 22 genes. While more comprehensive studies of this kind are ultimately required, this computational study demonstrates that models with similar training (reverse-engineering) error that have been inferred under varying degrees of a priori known topology information, exhibit considerably different predictive performance. This study was performed with a newly developed multiscale modeling and simulation tool called MultiGrain/MAPPER. [Copyright &y& Elsevier]

Abstract: This study applied a knowledge-driven data integration framework for the inference of protein–protein interactions (PPI). Evidence from diverse genomic features is integrated using a knowledge-driven Bayesian network (KD-BN). Receiver operating characteristic (ROC) curves may not be the optimal assessment method to evaluate a classifier''s performance in PPI prediction as the majority of the area under the curve (AUC) may not represent biologically meaningful results. It may be of benefit to interpret the AUC of a partial ROC curve whereby biologically interesting results are represented. Therefore, the novel application of the assessment method referred to as the partial ROC has been employed in this study to assess predictive performance of PPI predictions along with calculating the True positive/false positive rate and true positive/positive rate. By incorporating domain knowledge into the construction of the KD-BN, we demonstrate improvement in predictive performance compared with previous studies based upon the Naive Bayesian approach. [Copyright &y& Elsevier]