Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - WoS: 15Citation - Scopus: 15PriPath: 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, BurcuBackgroundCell 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 - Scopus: 3Prediction of Colorectal Cancer Based on Taxonomic Levels of Microorganisms and Discovery of Taxonomic Biomarkers Using the Grouping-Scoring (G-S-M) Approach(Elsevier Ltd, 2025-03) Bakir-Güngör, Burcu; Temiz, Mustafa; Canakcimaksutoglu, Beyza; Yousef, MalikColorectal cancer (CRC) is one of the most prevalent forms of cancer globally. The human gut microbiome plays an important role in the development of CRC and serves as a biomarker for early detection and treatment. This research effort focuses on the identification of potential taxonomic biomarkers of CRC using a grouping-based feature selection method. Additionally, this study investigates the effect of incorporating biological domain knowledge into the feature selection process while identifying CRC-associated microorganisms. Conventional feature selection techniques often fail to leverage existing biological knowledge during metagenomic data analysis. To address this gap, we propose taxonomy-based Grouping Scoring Modeling (G-S-M) method that integrates biological domain knowledge into feature grouping and selection. In this study, using metagenomic data related to CRC, classification is performed at three taxonomic levels (genus, family and order). The MetaPhlAn tool is employed to determine the relative abundance values of species in each sample. Comparative performance analyses involve six feature selection methods and four classification algorithms. When experimented on two CRC associated metagenomics datasets, the highest performance metric, yielding an AUC of 0.90, is observed at the genus taxonomic level. At this level, 7 out of top 10 groups (Parvimonas, Peptostreptococcus, Fusobacterium, Gemella, Streptococcus, Porphyromonas and Solobacterium) were commonly identified for both datasets. Moreover, the identified microorganisms at genus, family, and order levels are thoroughly discussed via refering to CRC-related metagenomic literature. This study not only contributes to our understanding of CRC development, but also highlights the applicability of taxonomy-based G-S-M method in tackling various diseases. © 2025 Elsevier B.V., All rights reserved.Article Citation - WoS: 9Citation - Scopus: 15MicroBiomeGSM: 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, MalikNumerous 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: 37Citation - Scopus: 43Inflammatory 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, HilalThe 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.Conference Object Citation - Scopus: 5Identifying Taxonomic Biomarkers of Colorectal Cancer in Human Intestinal Microbiota Using Multiple Feature Selection Methods(Institute of Electrical and Electronics Engineers Inc., 2022-09-07) Jabeer, Amhar; Kocak, Aysegul; Akkaş, Huseyin; Yenisert, Ferhan; Nalbantoĝlu, Özkan Ufuk; Yousef, Malik; Bakir-Güngör, Burcu; Bakir Gungor, BurcuA variety of bacterial species called gut microbiota work together to maintain a steady intestinal environment. The gastrointestinal tract contains tremendous amount of different species including archaea, bacteria, fungi, and viruses. While these organisms are crucial immune system stabilizers, the dysbiosis of the intestinal flora has been related to gastrointestinal disorders including Colorectal cancer (CRC), intestinal cancer, irritable bowel syndrome and inflammatory bowel disease. In the last decade, next-generation sequencing (NGS) methods have accelerated the identification of human gut flora. CRC is a deathly condition that has been on the rise in the last century, affecting half a million people each year. Since early CRC diagnosis is critical for an effective treatment, there is an immediate requirement for a classification system that can expedite CRC diagnosis. In this study, via analyzing the available metagenomics data on CRC, we aim to facilitate the CRC diagnosis via finding biomarkers linked with CRC, and via building a classification model. We have obtained the metagenomic sequencing data of the healthy individuals and CRC patients from a metagenome-wide association analysis and we have classified this data according to the disease stages. Conditional Mutual Information Maximization (CMIM), Fast Correlation Based Filter (FCBF), Extreme Gradient Boosting (XGBoost), min redundancy max relevance (mRMR), Information Gain (IG) and Select K Best (SKB) feature selection algorithms were utilized to cope with the complexity of the features. We observed that the SKB, IG, and XGBoost techniques made significant contributions to decrease the microbiota in use for CRC diagnosis, thereby reducing cost and time. We realized that our Random Forest classifier outperformed Adaboost, Support Vector Machine, Decision Tree, Logitboost and stacking ensemble classifiers in terms of CRC classification performance. Our results reiterated some known and some potential microbiome associated mechanisms in CRC, which could aid the design of new diagnostics based on the microbiome. © 2022 Elsevier B.V., All rights reserved.Article Citation - Scopus: 5Hyperplastic and Tubular Polyp Classification Using Machine Learning and Feature Selection(Elsevier B.V., 2024) Doǧan, Refika Sultan; Akay, Ebru; Doǧan, Serkan; Yilmaz, BulentPurpose: The aim of this study is to develop an effective approach for differentiating between hyperplastic and tubular adenoma colon polyps, which is one of the most difficult tasks in colonoscopy procedures. The main research challenge is how to improve the classification of these polyp subtypes applying various focusing levels on the polyp images, data preprocessing approaches, and classification algorithms. Methods: This study employed 202 colonoscopy videos from a total of 201 patients, focusing on 59 videos containing hyperplastic and tubular adenoma polyps. Manually extract key frames and several feature extraction and classification techniques were applied. The influence of different datasets with various focuses as well as data preprocessing steps on the performance of classification was examined, and AUC values were calculated using ten classifiers. Results: The study discovered that the optimal dataset, data preprocessing method, and classification algorithm all had significant effects on classification results. The Random Forest model with the Recursive Feature Elimination (RFE) feature selection approach, for example, consistently outperformed other models and achieved the highest AUC value of 0.9067. In terms of accuracy, F1 score, recall, and AUC, the suggested model outperformed a gastroenterologist, nevertheless precision remained slightly lower. Conclusion: This study emphasizes the importance of dataset selection, data preprocessing, and feature selection in enhancing the classification of difficult colon polyp subtypes. The suggested model offers a promising model for the clinical differentiation of hyperplastic and tubular adenoma polyps, potentially improving diagnostic accuracy in gastroenterology. © 2024 Elsevier B.V., All rights reserved.Article Citation - WoS: 16Citation - Scopus: 21GeNetOntology: Identifying Affected Gene Ontology Terms via Grouping, Scoring, and Modeling of Gene Expression Data Utilizing Biological Knowledge-Based Machine Learning(Frontiers Media S.A., 2023-08-21) Ersoz, Nur Sebnem; Bakir-Gungor, Burcu; Yousef, MalikIntroduction: Identifying significant sets of genes that are up/downregulated under specific conditions is vital to understand disease development mechanisms at the molecular level. Along this line, in order to analyze transcriptomic data, several computational feature selection (i.e., gene selection) methods have been proposed. On the other hand, uncovering the core functions of the selected genes provides a deep understanding of diseases. In order to address this problem, biological domain knowledge-based feature selection methods have been proposed. Unlike computational gene selection approaches, these domain knowledge-based methods take the underlying biology into account and integrate knowledge from external biological resources. Gene Ontology (GO) is one such biological resource that provides ontology terms for defining the molecular function, cellular component, and biological process of the gene product.Methods: In this study, we developed a tool named GeNetOntology which performs GO-based feature selection for gene expression data analysis. In the proposed approach, the process of Grouping, Scoring, and Modeling (G-S-M) is used to identify significant GO terms. GO information has been used as the grouping information, which has been embedded into a machine learning (ML) algorithm to select informative ontology terms. The genes annotated with the selected ontology terms have been used in the training part to carry out the classification task of the ML model. The output is an important set of ontologies for the two-class classification task applied to gene expression data for a given phenotype.Results: Our approach has been tested on 11 different gene expression datasets, and the results showed that GeNetOntology successfully identified important disease-related ontology terms to be used in the classification model.Discussion: GeNetOntology will assist geneticists and scientists to identify a range of disease-related genes and ontologies in transcriptomic data analysis, and it will also help doctors design diagnosis platforms and improve patient treatment plans.Conference Object Citation - WoS: 23Citation - Scopus: 52Evaluation of Classification Algorithms, Linear Discriminant Analysis and a New Hybrid Feature Selection Methodology for the Diagnosis of Coronary Artery Disease(Institute of Electrical and Electronics Engineers Inc., 2018-12) Kolukisa, Burak; Hacilar, Hilal; Göy, Gökhan; Kus, Mustafa; Bakir-Güngör, Burcu; Aral, Atilla; Güngör, Vehbi ÇağrıAccording to the World Health Organization (WHO), 31% of the world's total deaths in 2016 (17.9 million) was due to cardiovascular diseases (CVD). With the development of information technologies, it has become possible to predict whether people have heart diseases or not by checking certain physical and biochemical values at a lower cost. In this study, we have evalated a set of different classification algorithms, linear discriminant analysis and proposed a new hybrid feature selection methodology for the diagnosis of coronary heart diseases (CHD). Throughout this research effort, using three publicly available Heart Disease diagnosis datasets (UCI Machine Learning Repository), we have conducted comparative performance evaluations in terms of accuracy, sensitivity, specificity, F-measure, AUC and running time. © 2023 Elsevier B.V., All rights reserved.Article Citation - WoS: 41Citation - Scopus: 69Ensemble Feature Selection and Classification Methods for Machine Learning-Based Coronary Artery Disease Diagnosis(Elsevier, 2023-03) Kolukisa, Burak; Bakir-Gungor, BurcuCoronary artery disease (CAD) is a condition in which the heart is not fed sufficiently as a result of the accumulation of fatty matter. As reported by the World Health Organization, around 32% of the total deaths in the world are caused by CAD, and it is estimated that approximately 23.6 million people will die from this disease in 2030. CAD develops over time, and the diagnosis of this disease is difficult until a blockage or a heart attack occurs. In order to bypass the side effects and high costs of the current methods, researchers have proposed to diagnose CADs with computer-aided systems, which analyze some physical and biochemical values at a lower cost. In this study, for the CAD diagnosis, (i) seven different computational feature selection (FS) methods, one domain knowledge-based FS method, and different classification algorithms have been evaluated; (ii) an exhaustive ensemble FS method and a probabilistic ensemble FS method have been proposed. The proposed approach is tested on three publicly available CAD data sets using six different classification algorithms and four different variants of voting algorithms. The performance metrics have been comparatively evaluated with numerous combinations of classifiers and FS methods. The multi-layer perceptron classifier obtained satisfactory results on three data sets. Performance evaluations show that the proposed approach resulted in 91.78%, 85.55%, and 85.47% accuracy for the Z-Alizadeh Sani, Statlog, and Cleveland data sets, respectively.Article Citation - WoS: 7Citation - Scopus: 5Effect of Interpolation on Specular Reflections in Texture-Based Automatic Colonic Polyp Detection(Wiley, 2020-06-26) Kacmaz, Rukiye Nur; Yilmaz, Bulent; Aydin, ZaferReflections of LED light cause unwanted noise effects called specular reflection (SR) on colonoscopic images. The aim of this study was to seek answers to the following two questions. (a) How are the texture features used in automatic detection of polyps affected by the interpolation on specular reflections? (b) If they are affected does it really affect the classification performance? In order to answer these questions, we used 610 colonoscopy images, and divided each image into tiles whose sizes were 32-by-32 pixels. From these tiles, we selected the ones without any specular reflection. We added different shape and size specular reflections cropped from real images onto the reflection-free tiles. We then used the nearest neighbors, bilinear and bicubic interpolation techniques on the tiles on which SRs were added. On these tiles we extracted 116 texture features using 3 second-order approaches, and 4 first-order statistics. First, we used paired samplettest. Second, we performed automatic classification of polyps and background using random forest and k nearest neighbors (k-NN) approaches using the texture features for different combinations of specular reflections added on the tiles from the polyp or background. The results showed that depending on the size of specular reflection, interpolation can cause a significant difference between the texture features that were coming from reflection-free tiles and the same tiles on which interpolation was performed. In addition, we note that bicubic interpolation may be preferred to eliminate specular reflection when texture features are used for background and polyp discrimination.