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  • Article
    Citation - WoS: 26
    Citation - Scopus: 33
    miRmoduleNet: Detecting miRNA-mRNA Regulatory Modules
    (Frontiers Media S.A., 2022-04-12) Yousef, Malik; Goy, Gokhan; Bakir-Gungor, Burcu
    Increasing evidence that MicroRNAs (miRNAs) play a key role in carcinogenesis has revealed the need for elucidating the mechanisms of miRNA regulation and the roles of miRNAs in gene-regulatory networks. A better understanding of the interactions between miRNAs and their mRNA targets will provide a better understanding of the complex biological processes that occur during carcinogenesis. Increased efforts to reveal these interactions have led to the development of a variety of tools to detect and understand these interactions. We have recently described a machine learning approach miRcorrNet, based on grouping and scoring (ranking) groups of genes, where each group is associated with a miRNA and the group members are genes with expression patterns that are correlated with this specific miRNA. The miRcorrNet tool requires two types of -omics data, miRNA and mRNA expression profiles, as an input file. In this study we describe miRModuleNet, which groups mRNA (genes) that are correlated with each miRNA to form a star shape, which we identify as a miRNA-mRNA regulatory module. A scoring procedure is then applied to each module to further assess their contribution in terms of classification. An important output of miRModuleNet is that it provides a hierarchical list of significant miRNA-mRNA regulatory modules. miRModuleNet was further validated on external datasets for their disease associations, and functional enrichment analysis was also performed. The application of miRModuleNet aids the identification of functional relationships between significant biomarkers and reveals essential pathways involved in cancer pathogenesis.
  • Conference Object
    The Effect of Different Classifiers on Recursive Cluster Elimination in the Analysis of Transcriptomic Data
    (Institute of Electrical and Electronics Engineers Inc., 2023-10-11) Bulut, Nurten; Bakir-Güngör, Burcu; Qaqish, Bahjat F.; Yousef, Malik
    Gene expression data with limited sample size and a large number of genes are frequently encountered in genetic studies. In such high-dimensional data, identification of genes that distinguish between disease states is a challenging task. Feature selection (FS) is a useful approach in dealing with high dimensionality. Support Vector Machines Recursive Cluster Elimination (SVM-RCE) is a technique for FS in high-dimensional data. The SVM-RCE approach has been utilized for identification of clusters of genes whose expression levels correlate with pathological state. A key step in SVM-RCE is the use of an SVM classifier to assign an area under the curve (AUC) score to each gene cluster based on its ability to predict class labels. In this study, we investigate the use of alternative classifiers in the cluster-scoring step. Specifically, we compare Support Vector Machines, Random Forest, XgBoost, Naive Bayes, and linear logistic regression. In addition to AUC score performance evaluation, the algorithms are compared in terms of the number of selected genes at different levels of clustering and in terms of the running time. © 2023 Elsevier B.V., All rights reserved.
  • Article
    Citation - WoS: 6
    Citation - Scopus: 7
    The Determination of Distinctive Single Nucleotide Polymorphism Sets for the Diagnosis of Behcet's Disease
    (IEEE Computer Soc, 2022-05-01) Isik, Yunus Emre; Gormez, Yasin; Aydin, Zafer; Bakir-Gungor, Burcu
    Behcet's Disease (BD) is a multi-system inflammatory disorder in which the etiology remains unclear. The most probable hypothesis is that genetic tendency and environmental factors play roles in the development of BD. In order to find the essential reasons, genetic changes on thousands of genes should be analyzed. Besides, there is a need for extra analysis to find out which genetic factor affects the disease. Machine learning approaches have high potential for extracting the knowledge from genomics and selecting the representative Single Nucleotide Polymorphisms (SNPs) as the most effective features for the clinical diagnosis process. In this study, we have attempted to identify representative SNPs using feature selection methods, incorporating biological information and aimed to develop a machine-learning model for diagnosing Behcet's disease. By combining biological information and machine learning classifiers, up to 99.64 percent accuracy of disease prediction is achieved using only 13,611 out of 311,459 SNPs. In addition, we revealed the SNPs that are most distinctive by performing repeated feature selection in cross-validation experiments.
  • Article
    Citation - WoS: 10
    Citation - Scopus: 15
    Textnettopics Pro, a Topic Model-Based Text Classification for Short Text by Integration of Semantic and Document-Topic Distribution Information
    (Frontiers Media S.A., 2023-10-05) Voskergian, Daniel; Bakir-Gungor, Burcu; Yousef, Malik
    With the exponential growth in the daily publication of scientific articles, automatic classification and categorization can assist in assigning articles to a predefined category. Article titles are concise descriptions of the articles' content with valuable information that can be useful in document classification and categorization. However, shortness, data sparseness, limited word occurrences, and the inadequate contextual information of scientific document titles hinder the direct application of conventional text mining and machine learning algorithms on these short texts, making their classification a challenging task. This study firstly explores the performance of our earlier study, TextNetTopics on the short text. Secondly, here we propose an advanced version called TextNetTopics Pro, which is a novel short-text classification framework that utilizes a promising combination of lexical features organized in topics of words and topic distribution extracted by a topic model to alleviate the data-sparseness problem when classifying short texts. We evaluate our proposed approach using nine state-of-the-art short-text topic models on two publicly available datasets of scientific article titles as short-text documents. The first dataset is related to the Biomedical field, and the other one is related to Computer Science publications. Additionally, we comparatively evaluate the predictive performance of the models generated with and without using the abstracts. Finally, we demonstrate the robustness and effectiveness of the proposed approach in handling the imbalanced data, particularly in the classification of Drug-Induced Liver Injury articles as part of the CAMDA challenge. Taking advantage of the semantic information detected by topic models proved to be a reliable way to improve the overall performance of ML classifiers.
  • Article
    Citation - WoS: 48
    Citation - Scopus: 65
    Review of Feature Selection Approaches Based on Grouping of Features
    (PeerJ Inc, 2023-07-17) Kuzudisli, Cihan; Bakir-Gungor, Burcu; Bulut, Nurten; Qaqish, Bahjat; Yousef, Malik
    With the rapid development in technology, large amounts of high-dimensional data have been generated. This high dimensionality including redundancy and irrelevancy poses a great challenge in data analysis and decision making. Feature selection (FS) is an effective way to reduce dimensionality by eliminating redundant and irrelevant data. Most traditional FS approaches score and rank each feature individually; and then perform FS either by eliminating lower ranked features or by retaining highly -ranked features. In this review, we discuss an emerging approach to FS that is based on initially grouping features, then scoring groups of features rather than scoring individual features. Despite the presence of reviews on clustering and FS algorithms, to the best of our knowledge, this is the first review focusing on FS techniques based on grouping. The typical idea behind FS through grouping is to generate groups of similar features with dissimilarity between groups, then select representative features from each cluster. Approaches under supervised, unsupervised, semi supervised and integrative frameworks are explored. The comparison of experimental results indicates the effectiveness of sequential, optimization-based (i.e., fuzzy or evolutionary), hybrid and multi-method approaches. When it comes to biological data, the involvement of external biological sources can improve analysis results. We hope this work's findings can guide effective design of new FS approaches using feature grouping.
  • Article
    Citation - Scopus: 25
    Recursive Cluster Elimination Based Rank Function (SVM-RCE-R) Implemented in KNIME
    (F1000 Research Ltd, 2021-01-05) Yousef, Malik; Bakir-Güngör, Burcu; Jabeer, Amhar; Göy, Gökhan; Qureshi, Rehman A.; C Showe, Louise; C. Showe, Louise
    In our earlier study, we proposed a novel feature selection approach, Recursive Cluster Elimination with Support Vector Machines (SVM-RCE) and implemented this approach in Matlab. Interest in this approach has grown over time and several researchers have incorporated SVM-RCE into their studies, resulting in a substantial number of scientific publications. This increased interest encouraged us to reconsider how feature selection, particularly in biological datasets, can benefit from considering the relationships of those genes in the selection process, this led to our development of SVM-RCE-R. SVM-RCE-R, further enhances the capabilities of SVM-RCE by the addition of a novel user specified ranking function. This ranking function enables the user to stipulate the weights of the accuracy, sensitivity, specificity, f-measure, area under the curve and the precision in the ranking function This flexibility allows the user to select for greater sensitivity or greater specificity as needed for a specific project. The usefulness of SVM-RCE-R is further supported by development of the maTE tool which uses a similar approach to identify MicroRNA (miRNA) targets. We have also now implemented the SVM-RCE-R algorithm in Knime in order to make it easier to applyThe use of SVM-RCE-R in Knime is simple and intuitive and allows researchers to immediately begin their analysis without having to consult an information technology specialist. The input for the Knime implemented tool is an EXCEL file (or text or CSV) with a simple structure and the output is also an EXCEL file. The Knime version also incorporates new features not available in SVM-RCE. The results show that the inclusion of the ranking function has a significant impact on the performance of SVM-RCE-R. Some of the clusters that achieve high scores for a specified ranking can also have high scores in other metrics. © 2021 Elsevier B.V., All rights reserved.
  • Article
    Citation - WoS: 15
    Citation - Scopus: 15
    PriPath: Identifying Dysregulated Pathways From Differential Gene Expression via Grouping, Scoring, and Modeling With an Embedded Feature Selection Approach
    (BMC, 2023-02-23) Yousef, Malik; Ozdemir, Fatma; Jaber, Amhar; Allmer, Jens; Bakir-Gungor, Burcu
    BackgroundCell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an organism. The Kyoto encyclopedia of genes and genomes (KEGG) systematically analyzes gene functions, proteins, and molecules and combines them into pathways. Measurements of gene expression (e.g., RNA-seq data) can be mapped to KEGG pathways to determine which modules are affected or dysregulated in the disease. However, genes acting in multiple pathways and other inherent issues complicate such analyses. Many current approaches may only employ gene expression data and need to pay more attention to some of the existing knowledge stored in KEGG pathways for detecting dysregulated pathways. New methods that consider more precompiled information are required for a more holistic association between gene expression and diseases.ResultsPriPath is a novel approach that transfers the generic process of grouping and scoring, followed by modeling to analyze gene expression with KEGG pathways. In PriPath, KEGG pathways are utilized as the grouping function as part of a machine learning algorithm for selecting the most significant KEGG pathways. A machine learning model is trained to differentiate between diseases and controls using those groups. We have tested PriPath on 13 gene expression datasets of various cancers and other diseases. Our proposed approach successfully assigned biologically and clinically relevant KEGG terms to the samples based on the differentially expressed genes. We have comparatively evaluated the performance of PriPath against other tools, which are similar in their merit. For each dataset, we manually confirmed the top results of PriPath in the literature and found that most predictions can be supported by previous experimental research.ConclusionsPriPath can thus aid in determining dysregulated pathways, which applies to medical diagnostics. In the future, we aim to advance this approach so that it can perform patient stratification based on gene expression and identify druggable targets. Thereby, we cover two aspects of precision medicine.
  • Article
    Citation - WoS: 9
    Citation - Scopus: 15
    MicroBiomeGSM: The Identification of Taxonomic Biomarkers From Metagenomic Data Using Grouping, Scoring and Modeling (G-S-M) Approach
    (Frontiers Media S.A., 2023-11-22) Bakir-Gungor, Burcu; Temiz, Mustafa; Jabeer, Amhar; Wu, Di; Yousef, Malik
    Numerous biological environments have been characterized with the advent of metagenomic sequencing using next generation sequencing which lays out the relative abundance values of microbial taxa. Modeling the human microbiome using machine learning models has the potential to identify microbial biomarkers and aid in the diagnosis of a variety of diseases such as inflammatory bowel disease, diabetes, colorectal cancer, and many others. The goal of this study is to develop an effective classification model for the analysis of metagenomic datasets associated with different diseases. In this way, we aim to identify taxonomic biomarkers associated with these diseases and facilitate disease diagnosis. The microBiomeGSM tool presented in this work incorporates the pre-existing taxonomy information into a machine learning approach and challenges to solve the classification problem in metagenomics disease-associated datasets. Based on the G-S-M (Grouping-Scoring-Modeling) approach, species level information is used as features and classified by relating their taxonomic features at different levels, including genus, family, and order. Using four different disease associated metagenomics datasets, the performance of microBiomeGSM is comparatively evaluated with other feature selection methods such as Fast Correlation Based Filter (FCBF), Select K Best (SKB), Extreme Gradient Boosting (XGB), Conditional Mutual Information Maximization (CMIM), Maximum Likelihood and Minimum Redundancy (MRMR) and Information Gain (IG), also with other classifiers such as AdaBoost, Decision Tree, LogitBoost and Random Forest. microBiomeGSM achieved the highest results with an Area under the curve (AUC) value of 0.98% at the order taxonomic level for IBDMD dataset. Another significant output of microBiomeGSM is the list of taxonomic groups that are identified as important for the disease under study and the names of the species within these groups. The association between the detected species and the disease under investigation is confirmed by previous studies in the literature. The microBiomeGSM tool and other supplementary files are publicly available at: https://github.com/malikyousef/microBiomeGSM.
  • Article
    Citation - WoS: 29
    Citation - Scopus: 32
    Liver Fibrosis Staging Using CT Image Texture Analysis and Soft Computing
    (Elsevier, 2014-12) Kayaalti, Omer; Aksebzeci, Bekir Hakan; Karahan, Ibrahim Okkes; Deniz, Kemal; Ozturk, Mehmet; Yilmaz, Bulent; Asyali, Musa Hakan
    Liver biopsy is considered to be the gold standard for analyzing chronic hepatitis and fibrosis; however, it is an invasive and expensive approach, which is also difficult to standardize. Medical imaging techniques such as ultrasonography, computed tomography (CT), and magnetic resonance imaging are non-invasive and helpful methods to interpret liver texture, and may be good alternatives to needle biopsy. Recently, instead of visual inspection of these images, computer-aided image analysis based approaches have become more popular. In this study, a non-invasive, low-cost and relatively accurate method was developed to determine liver fibrosis stage by analyzing some texture features of liver CT images. In this approach, some suitable regions of interests were selected on CT images and a comprehensive set of texture features were obtained from these regions using different methods, such as Gray Level Co-occurrence matrix (GLCM), Laws' method, Discrete Wavelet Transform (DWT), and Gabor filters. Afterwards, sequential floating forward selection and exhaustive search methods were used in various combinations for the selection of most discriminating features. Finally, those selected texture features were classified using two methods, namely, Support Vector Machines (SVM) and k-nearest neighbors (k-NN). The mean classification accuracy in pairwise group comparisons was approximately 95% for both classification methods using only 5 features. Also, performance of our approach in classifying liver fibrosis stage of subjects in the test set into 7 possible stages was investigated. In this case, both SVM and k-NN methods have returned relatively low classification accuracies. Our pairwise group classification results showed that DWT, Gabor, GLCM, and Laws' texture features were more successful than the others; as such features extracted from these methods were used in the feature fusion process. Fusing features from these better performing families further improved the classification performance. The results show that our approach can be used as a decision support system in especially pairwise fibrosis stage comparisons. (C) 2014 Elsevier B.V. All rights reserved.
  • Article
    Citation - WoS: 35
    Citation - Scopus: 42
    Inflammatory Bowel Disease Biomarkers of Human Gut Microbiota Selected via Different Feature Selection Methods
    (PeerJ Inc, 2022-04-25) Bakir-Gungor, Burcu; Lar, Hilal Hac; Jabeer, Amhar; Nalbantoglu, Ozkan Ufuk; Aran, Oya; Yousef, Malik; Hacilar, Hilal
    The tremendous boost in next generation sequencing and in the "omics" technologies makes it possible to characterize the human gut microbiome-the collective genomes of the microbial community that reside in our gastrointestinal tract. Although some of these microorganisms are considered to be essential regulators of our immune system, the alteration of the complexity and eubiotic state of microbiota might promote autoimmune and inflammatory disorders such as diabetes, rheumatoid arthritis, Inflammatory bowel diseases (IBD), obesity, and carcinogenesis. IBD, comprising Crohn's disease and ulcerative colitis, is a gut-related, multifactorial disease with an unknown etiology. IBD presents defects in the detection and control of the gut microbiota, associated with unbalanced immune reactions, genetic mutations that confer susceptibility to the disease, and complex environmental conditions such as westernized lifestyle. Although some existing studies attempt to unveil the composition and functional capacity of the gut microbiome in relation to IBD diseases, a comprehensive picture of the gut microbiome in IBD patients is far from being complete. Due to the complexity of metagenomic studies, the applications of the state-of-the-art machine learning techniques became popular to address a wide range of questions in the field of metagenomic data analysis. In this regard, using IBD associated metagenomics dataset, this study utilizes both supervised and unsupervised machine learning algorithms, (i) to generate a classification model that aids IBD diagnosis, (ii) to discover IBD-associated biomarkers, (iii) to discover subgroups of IBD patients using k-means and hierarchical clustering approaches. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization (CMIM), Fast Correlation Based Filter (FCBF), min redundancy max relevance (mRMR), Select K Best (SKB), Information Gain (IG) and Extreme Gradient Boosting (XGBoost). In our experiments with 100-fold Monte Carlo cross-validation (MCCV), XGBoost, IG, and SKB methods showed a considerable effect in terms of minimizing the microbiota used for the diagnosis of IBD and thus reducing the cost and time. We observed that compared to Decision Tree, Support Vector Machine, Logitboost, Adaboost, and stacking ensemble classifiers, our Random Forest classifier resulted in better performance measures for the classification of IBD. Our findings revealed potential microbiome-mediated mechanisms of IBD and these findings might be useful for the development of microbiome-based diagnostics.