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Journal of Supercomputing (15730484) 81(5)
The importance of a node, known as centrality, can be defined and measured in various ways. The main challenge of these measurements is their extension to multilayer networks. In multilayer networks, the influence of inter-layer edges compared to intra-layer edges must be considered when calculating centrality measures. Here, the primary purpose is to provide a multilayer network-specific framework to measure the importance of nodes, with special consideration for inter-layer edges and intra-layer ones. First, we considered the different centrality measures offered for multilayer networks, as well as the associated tools and packages. Next, we implemented some more informative measures specific to multilayer networks. The functionality of implemented metrics is provided for some real networks using Python. We assessed these metrics as ranking criteria and then contrasted the ranking results using three methods: intersection similarity, rank differences, and Kendall’s tau. The findings demonstrated that incorporating information from various layers enhances the effectiveness of the criteria. The final product is a publicly available Python package called MultiNetPy, available at https://github.com/Multinetpy/Multinetpy. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
Data in Brief (23523409) 61
Circular RNAs (circRNAs) are a type of RNAs that play crucial roles in various biological processes. Their outstanding properties such as tissue-specific expression and high resistance to exonuclease degradation make them attractive for research. However, a comprehensive analysis tool for analyzing circRNA data is still required. Here, we present CircPac, a newly developed web-based toolset that searches databases like circBase, circBank, and circRNADisease and organizes data to provide and visualize circRNAs information. Our toolset was created using the Python programming language and its libraries, such as pandas, seaborn, and the Django framework. CircPac enables users to unify the circRNA IDs and subsequently perform various bioinformatic analyses. These analyses include retrieving basic circRNA information, identifying target miRNAs, and analyzing circRNA expression changes in various diseases. Additionally, this toolset generates ready-to-publish figures of circRNA-miRNA interactions and circRNAs expression changes in diseases. CircPac is freely accessible (at https://www.circpac.ir) and offers a user-friendly platform for biologists to efficiently conduct and visualize circRNA data analyses in an appropriate format. © 2025 The Authors
Biochemistry and Biophysics Reports (24055808) 41
Introduction: Gastric cancer (GC) is among the deadliest malignancies globally, characterized by hypoxia-driven pathways that promote cancer progression, including stemness mechanisms facilitating invasion and metastasis. This study aimed to develop a prognostic decision tree using genes implicated in hypoxia and stemness pathways to predict outcomes in GC patients. Materials and methods: GC RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed to compute hypoxia and stemness scores using Gene Set Variation Analysis (GSVA) and the mRNA expression-based stemness index (mRNAsi). Hierarchical clustering identified clusters with distinct survival outcomes, and differentially expressed genes (DEGs) between clusters were identified. Weighted Gene Co-expression Network Analysis (WGCNA) identified modules and hub genes associated with clinical traits. Overlapping DEGs and hub genes underwent functional enrichment, protein-protein interaction (PPI) network analysis, and survival analysis. A prognostic decision tree was constructed using survival-associated shared genes. Results: Hierarchical clustering identified six clusters among 375 TCGA GC patients, with significant survival differences between cluster 1 (low hypoxia, high stemness) and cluster 4 (high hypoxia, high stemness). Validation in the GSE62254 dataset corroborated these findings. WGCNA revealed modules linked to clinical traits and survival, with functional enrichment highlighting pathways like cell adhesion and calcium signaling. The decision tree, based on genes such as AKAP6, GLRB, and RUNX1T1, achieved an AUC of 0.81 (training) and 0.67 (test), demonstrating the utility of combined scores in patient stratification. Conclusion: This study introduces a novel hypoxia-stemness-based prognostic decision tree for GC. The identified genes show promise as prognostic biomarkers, warranting further clinical validation. © 2024 The Authors
Pattern Analysis and Applications (1433755X) 26(4)pp. 1715-1727
Clinical notes contain valuable patient information. These notes are written by health care providers with various scientific levels and writing styles. It might be helpful for clinicians and researchers to understand what information is essential when dealing with extensive electronic medical records. Entities recognizing them and mapping them to standard terminologies is crucial to reducing ambiguity in processing clinical notes. Although named entity recognition and entity linking are critical steps in clinical natural language processing, they can produce repetitive and low-value concepts. On the other hand, all parts of a clinical text do not share the same importance or content in predicting the patient's condition. As a result, it is necessary to identify the section in which each content item is recorded and critical concepts to extract meaning from clinical texts. In this study, these challenges have been addressed by using clinical natural language processing techniques. In addition, a set of unsupervised essential phrase extraction methods has been verified and evaluated to identify key concepts. Considering that most clinical concepts are in the form of multi-word expressions and their accurate identification requires the user to specify an n-gram range, we have proposed a shortcut method to preserve the structure of the term based on TF-IDF (Term Frequency Inverse Document Frequency). To evaluate, we have designed two types of downstream tasks (multiple and binary classification) using the capabilities of transformer-based models. The results show the proposed method's superiority in combination with the SciBERT model. Also, they offer an insight into the efficacy of general methods for extracting essential phrases from clinical notes. © 2023, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.
Journal Of Cellular And Molecular Medicine (15821838) 27(5)pp. 714-726
DNA methylation is an early event in tumorigenesis. Here, by integrative analysis of DNA methylation and gene expression and utilizing machine learning approaches, we introduced potential diagnostic and prognostic methylation signatures for stomach cancer. Differentially-methylated positions (DMPs) and differentially-expressed genes (DEGs) were identified using The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) data. A total of 256 DMPs consisting of 140 and 116 hyper- and hypomethylated positions were identified between 443 tumour and 27 nontumour STAD samples. Gene expression analysis revealed a total of 2821 DEGs with 1247 upregulated and 1574 downregulated genes. By analysing the impact of cis and trans regulation of methylation on gene expression, a dominant negative correlation between methylation and expression was observed, while for trans regulation, in hypermethylated and hypomethylated genes, there was mainly a negative and positive correlation with gene expression, respectively. To find diagnostic biomarkers, we used 28 hypermethylated probes locating in the promoter of 27 downregulated genes. By implementing a feature selection approach, eight probes were selected and then used to build a support vector machine diagnostic model, which had an area under the curve of 0.99 and 0.97 in the training and validation (GSE30601 with 203 tumour and 94 nontumour samples) cohorts, respectively. Using 412 TCGA-STAD samples with both methylation and clinical data, we also identified four prognostic probes by implementing univariate and multivariate Cox regression analysis. In summary, our study introduced potential diagnostic and prognostic biomarkers for STAD, which demands further validation. © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Knowledge and Information Systems (02191377) 64(12)pp. 3293-3324
Patient similarity assessment, which identifies patients similar to a given patient, is a fundamental component of many secondary uses of medical data. The assessment can be performed using electronic medical records (EMRs). Patient similarity measurement requires converting heterogeneous EMRs into comparable formats to calculate distance. This study presents a new data representation method for EMRs that considers the information in clinical narratives. To address the limitations of previous approaches in handling complex parts of EMR data, an unsupervised manner is proposed for building a patient representation, which integrates unstructured and structured data extracted from patients' EMRs. We employed a tree structure to model the extracted data that capture the temporal relations of multiple medical events from EMR. We processed clinical notes to extract medical concepts using Python libraries such as MedspaCy and ScispaCy and mapped entities to the Unified Medical Language System (UMLS). To capture temporal aspects of the extracted events, we developed two new relabeling methods for the non-leaf nodes of the tree. To create an embedding vector for each patient, we traversed the tree to generate sequences that the Doc2vec algorithm would use. The comprehensive evaluation of the proposed method for patient similarity and mortality prediction tasks demonstrated that our proposed model leads to lower mean-squared error (MSE), higher precision, and normalized discounted cumulative gain (NDCG) relative to baselines. © 2022, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.
Sharifi, S. ,
Lotfi shahreza, M. ,
Pakdel, A. ,
Reecy, J.M. ,
Ghadiri, N. ,
Atashi, H. ,
Motamedi, M. ,
Ebrahimie, E. Animals (20762615) 12(1)
Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the leading agents causing acute severe infection with clinical signs. E. Coli, environmental mastitis pathogens, are the primary etiological agents of bovine mastitis in well-managed dairy farms. Response to E. Coli infection has a complex pattern affected by genetic and environmental parameters. On the other hand, the efficacy of antibiotics and/or anti-inflammatory treatment in E. coli mastitis is still a topic of scientific debate, and studies on the treatment of clinical cases show conflicting results. Unraveling the bio-signature of mastitis in dairy cattle can open new avenues for drug repurposing. In the current research, a novel, semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration, was used to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. Online data repositories relevant to known diseases, drugs, and gene targets, along with other specialized biological information for E. coli mastitis, including critical genes with robust bio-signatures, drugs, and related disorders, were used as input data for analysis with the Heter-LP algorithm. Our research identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or a combination of two or more active compounds to treat this infectious disease. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Journal of Biomedical Informatics (15320480) 115
One of the effective missions of biology and medical science is to find disease-related genes. Recent research uses gene/protein networks to find such genes. Due to false positive interactions in these networks, the results often are not accurate and reliable. Integrating multiple gene/protein networks could overcome this drawback, causing a network with fewer false positive interactions. The integration method plays a crucial role in the quality of the constructed network. In this paper, we integrate several sources to build a reliable heterogeneous network, i.e., a network that includes nodes of different types. Due to the different gene/protein sources, four gene-gene similarity networks are constructed first and integrated by applying the type-II fuzzy voter scheme. The resulting gene-gene network is linked to a disease-disease similarity network (as the outcome of integrating four sources) through a two-part disease-gene network. We propose a novel algorithm, namely random walk with restart on the heterogeneous network method with fuzzy fusion (RWRHN-FF). Through running RWRHN-FF over the heterogeneous network, disease-related genes are determined. Experimental results using the leave-one-out cross-validation indicate that RWRHN-FF outperforms existing methods. The proposed algorithm can be applied to find new genes for prostate, breast, gastric, and colon cancers. Since the RWRHN-FF algorithm converges slowly on large heterogeneous networks, we propose a parallel implementation of the RWRHN-FF algorithm on the Apache Spark platform for high-throughput and reliable network inference. Experiments run on heterogeneous networks of different sizes indicate faster convergence compared to other non-distributed modes of implementation. © 2021 Elsevier Inc.
Journal of Biomedical Informatics (15320480) 116
Automatic text summarization methods generate a shorter version of the input text to assist the reader in gaining a quick yet informative gist. Existing text summarization methods generally focus on a single aspect of text when selecting sentences, causing the potential loss of essential information. In this study, we propose a domain-specific method that models a document as a multi-layer graph to enable multiple features of the text to be processed at the same time. The features we used in this paper are word similarity, semantic similarity, and co-reference similarity, which are modelled as three different layers. The unsupervised method selects sentences from the multi-layer graph based on the MultiRank algorithm and the number of concepts. The proposed MultiGBS algorithm employs UMLS and extracts the concepts and relationships using different tools such as SemRep, MetaMap, and OGER. Extensive evaluation by ROUGE and BERTScore shows increased F-measure values. © 2021 Elsevier Inc.
Scientific Reports (20452322) 10(1)
Rare or orphan diseases affect only small populations, thereby limiting the economic incentive for the drug development process, often resulting in a lack of progress towards treatment. Drug repositioning is a promising approach in these cases, due to its low cost. In this approach, one attempts to identify new purposes for existing drugs that have already been developed and approved for use. By applying the process of drug repositioning to identify novel treatments for rare diseases, we can overcome the lack of economic incentives and make concrete progress towards new therapies. Adrenocortical Carcinoma (ACC) is a rare disease with no practical and definitive therapeutic approach. We apply Heter-LP, a new method of drug repositioning, to suggest novel therapeutic avenues for ACC. Our analysis identifies innovative putative drug-disease, drug-target, and disease-target relationships for ACC, which include Cosyntropin (drug) and DHCR7, IGF1R, MC1R, MAP3K3, TOP2A (protein targets). When results are analyzed using all available information, a number of novel predicted associations related to ACC appear to be valid according to current knowledge. We expect the predicted relations will be useful for drug repositioning in ACC since the resulting ranked lists of drugs and protein targets can be used to expedite the necessary clinical processes. © 2020, The Author(s).
Expert Systems with Applications (09574174) 159
Background and objective: Heterogeneous complex networks are large graphs consisting of different types of nodes and edges. The knowledge extraction from these networks is complicated. Moreover, the scale of these networks is steadily increasing. Thus, scalable methods are required. Methods: In this paper, two distributed label propagation algorithms for heterogeneous networks, namely DHLP-1 and DHLP-2 have been introduced. Biological networks are one type of the heterogeneous complex networks. As a case study, we have measured the efficiency of our proposed DHLP-1 and DHLP-2 algorithms on a biological network consisting of drugs, diseases, and targets. The subject we have studied in this network is drug repositioning but our algorithms can be used as general methods for heterogeneous networks other than the biological network. Results: We compared the proposed algorithms with similar non-distributed versions of them namely MINProp and Heter-LP. The experiments revealed the good performance of the algorithms in terms of running time and accuracy. © 2020 Elsevier Ltd
Methods in Molecular Biology (19406029) 1903pp. 291-316
Using existing drugs for diseases which are not developed for their treating (drug repositioning) provides a new approach to developing drugs at a lower cost, faster, and more secured. We proposed a method for drug repositioning which can predict simple and complex relationships between drugs, drug targets, and diseases. Since biological networks typically present a suitable model for relationships between different biological concepts, our primary approach is to analyze graphs and complex networks in the study of drugs and their therapeutic effects. Given the nature of existing data, the use of semi-supervised learning methods is crucial. So, in our research, we have developed a label propagation method to predict drug-target, drug-disease, and disease-target interactions (Heter-LP), which integrates various data sources at different levels. The predicted interactions are the most prominent relationships among the millions of relationships suggested to the related researchers for further investigation. The main advantages of Heter-LP are the effective integration of input data, eliminating the need for negative samples, and the use of local and global features together. The main steps of this research are as follows. The first step is the construction of a heterogeneous network as a data modeling task, in which data are collected and prepared. The second step is predicting potential interactions. We present a new label propagation algorithm for heterogeneous networks, which consists of two parts, one mapping and the other an iterative method for determining the final labels of the entire network vertices. Finally, for evaluation, we calculated the AUC and AUPR with tenfold cross-validation and compared the results with the best available methods for label propagation in heterogeneous networks and drug repositioning. Also, a series of experimental evaluations and some specific case studies have been presented. The result of the AUC and AUPR for Heter-LP was much higher than the average of the best available methods. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Briefings in Bioinformatics (14774054) 19(5)pp. 878-892
Experimental drug development is time-consuming, expensive and limited to a relatively small number of targets. However, recent studies show that repositioning of existing drugs can function more efficiently than de novo experimental drug development to minimize costs and risks. Previous studies have proven that network analysis is a versatile platform for this purpose, as the biological networks are used to model interactions between many different biological concepts. The present study is an attempt to review network-based methods in predicting drug targets for drug repositioning. For each method, the preferred type of data set is described, and their advantages and limitations are discussed. For each method, we seek to provide a brief description, as well as an evaluation based on its performance metrics.We conclude that integrating distinct and complementary data should be used because each type of data set reveals a unique aspect of information about an organism. We also suggest that applying a standard set of evaluation metrics and data sets would be essential in this fast-growing research domain.
Journal of Biomedical Informatics (15320480) 68pp. 167-183
Drug repositioning offers an effective solution to drug discovery, saving both time and resources by finding new indications for existing drugs. Typically, a drug takes effect via its protein targets in the cell. As a result, it is necessary for drug development studies to conduct an investigation into the interrelationships of drugs, protein targets, and diseases. Although previous studies have made a strong case for the effectiveness of integrative network-based methods for predicting these interrelationships, little progress has been achieved in this regard within drug repositioning research. Moreover, the interactions of new drugs and targets (lacking any known targets and drugs, respectively) cannot be accurately predicted by most established methods. In this paper, we propose a novel semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration. To predict drug-target, disease-target, and drug-disease associations, we use information about drugs, diseases, and targets as collected from multiple sources at different levels. Our algorithm integrates these various types of data into a heterogeneous network and implements a label propagation algorithm to find new interactions. Statistical analyses of 10-fold cross-validation results and experimental analyses support the effectiveness of the proposed algorithm. © 2017
Scientia Iranica (23453605) 18(6)pp. 1460-1468
Self-Organizing Maps (SOMs) are among the most well-known, unsupervised neural network approaches to clustering, which are very efficient in handling large and high dimensional datasets. The original Particle Swarm Optimization (PSO) is another algorithm discovered through simplified social model simulation, which is effective in nonlinear optimization problems and easy to implement. In the present study, we combine these two methods and introduce a new method for anomaly detection. A discussion about our method is presented, its results are compared with some other methods and its advantages over them are demonstrated. In order to apply our method, we also performed a case study on forest fire detection. Our algorithm was shown to be simple and to function better than previous ones. We can apply it to different domains of anomaly detection. In fact, we observed our method to be a generic algorithm for anomaly detection that may need few changes for implementation in different domains. © 2012 Sharif University of Technology. Production and hosting by Elsevier B.V. All rights reserved.
The correct use of constraints within relational DBMSs is essential for one to take full advantage of the significant benefits offered by the relational model. The use of formal descriptions to capture constraints early in the process may be appropriate in this regard. The theory of relational databases has much in common with the mathematical structures central to the Z notation. In this position paper, we describe how create suitable tables and sql code for Z specifications that have been made according to UML diagrams by Robert's methods[5].Here We use the Z notation as our specification language, and SQL as our implementation language. © 2009 IEEE.
