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Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/394

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Enhancing Complex Disease Group Scoring with Mirgedinet: A Multi-Algorithm Machine Learning Framework Based on the GSM Approach
(IEEE, 2025-06-25) Qumsiyeh, Emma; Bakir-Gungor, Burcu; Yousef, Malik
Integrating biological prior knowledge for disease gene associations has shown significant promise in discovering new biomarkers with potential translational applications. This work investigates the application of a multi-algorithm machine learning framework based on the Grouping-Scoring-Modeling (G-S-M) approach for improving the prediction of complex diseases. The study identifies the primary gene and miRNA interactions in various complex diseases with the help of miRGediNET, which is a machine-learning based tool that integrates data from three biological databases. Traditional methods have only focused on independence between features; the G-S-M method focuses on aggregating genes based on biological interactions, pinpointing the scoring of gene groups for a disease, and modeling its predictive capability using advanced machine learning algorithms. In this research paper, seven algorithms, including Support Vector Machine, Decision Tree, and CatBoost, were applied to eight datasets extracted from the GEO database. This framework proved very robust in ranking gene clusters, thus predicting critical biomarkers while doing 100-fold randomized cross-validation within the evaluation. The results indicate this approach's high potential for refining disease and supporting research for choosing the best algorithm that can provide biological insights and computational advances.
Correction: Engineering Novel Features for Diabetes Complication Prediction Using Synthetic Electronic Health Records
(Frontiers Media S.A., 2025-08-29) Voskergian, Daniel; Bakir-Gungor, Burcu; Yousef, Malik
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.
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.
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.
TextNetTopics+: Enhancing Text Classification Through Classifier Diversity and Model Ensembling
(Springer International Publishing AG, 2025) Voskergian, Daniel; Bakir-Gungor, Burcu; Yousef, Malik
TextNetTopics is an innovative text classification framework that integrates topic modeling with feature selection to improve model accuracy and interpretability. Unlike traditional methods that rely on individual words, TextNetTopics selects cohesive topics extracted via Latent Dirichlet Allocation as features for document representation, effectively reducing dimensionality while preserving the semantic structure of the text. This study evaluates the performance of TextNetTopics utilizing multiple machine learning algorithms in the M (Modeling) component, including Random Forest, Support Vector Machine, Gradient Boosting, eXtreme Gradient Boosting, and Logistic Regression. To further enhance classification performance, we introduce TextNetTopics+, an ensemblebased extension that leverages both hard voting and soft voting mechanisms to combine the strengths of multiple classifiers. Comprehensive experiments on the LitCovid and WOS datasets demonstrate that ensemble learning in TextNetTopics + significantly outperforms individual classifiers in TextNetTopics, confirming its effectiveness in improving model robustness and generalization.
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.
Citation - WoS: 2
Citation - Scopus: 4
RCE-IFE: Recursive Cluster Elimination With Intra-Cluster Feature Elimination
(PeerJ Inc, 2025-02-07) Kuzudisli, Cihan; Bakir-Gungor, Burcu; Qaqish, Bahjat; Yousef, Malik
The computational and interpretational difficulties caused by the ever-increasing dimensionality of biological data generated by new technologies pose a significant challenge. Feature selection (FS) methods aim to reduce the dimension, and feature grouping has emerged as a foundation for FS techniques that seek to detect strong correlations among features and identify irrelevant features. In this work, we propose the Recursive Cluster Elimination with Intra-Cluster Feature Elimination (RCE-IFE) method that utilizes feature grouping and iterates grouping and elimination steps in a supervised context. We assess dimensionality reduction and discriminatory capabilities of RCE-IFE on various high-dimensional datasets from different biological domains. For a set of gene expression, MicroRNA (miRNA) expression, and methylation datasets, the performance of RCE-IFE is comparatively evaluated with RCE-IFE-SVM (the SVM-adapted version of RCE-IFE) and SVM-RCE. On average, RCE-IFE attains an area under the curve (AUC) of 0.85 among tested expression datasets with the fewest features and the shortest running time, while RCE-IFE-SVM (the SVM-adapted version of RCE-IFE) and SVM-RCE achieve similar AUCs of 0.84 and 0.83, respectively. RCE-IFE and SVM-RCE yield AUCs of 0.79 and 0.68, respectively when averaged over seven different metagenomics datasets, with RCE-IFE significantly reducing feature subsets. Furthermore, RCE-IFE surpasses several state-of-the-art FS methods, such as Minimum Redundancy Maximum Relevance (MRMR), Fast Correlation-Based Filter (FCBF), Information Gain (IG), Conditional Mutual Information Maximization (CMIM), SelectKBest (SKB), and eXtreme Gradient Boosting (XGBoost), obtaining an average AUC of 0.76 on five gene expression datasets. Compared with a similar tool, Multi-stage, RCE-IFE gives a similar average accuracy rate of 89.27% using fewer features on four cancer-related datasets. The comparability of RCE-IFE is also verified with other biological domain knowledge-based Grouping-Scoring-Modeling (G-S-M) tools, including mirGediNET, 3Mint, and miRcorrNet. Additionally, the biological relevance of the selected features by RCE-IFE is evaluated. The proposed method also exhibits high consistency in terms of the selected features across multiple runs. Our experimental findings imply that RCE-IFE provides robust classifier performance and significantly reduces feature size while maintaining feature relevance and consistency.
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.
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.

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