Browsing by Author "Yousef, Malik"

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Hastalık Tahmini ve Biyobelirteçlerin Tespiti için Makine Öğrenim Modellerinin Tasarımı ve Geliştirilmesi
(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2024) Temiz, Mustafa; Güngör, Burcu; Yousef, Malik
In medical science, the prediction of diseases and the identification of biomarkers play an important role in the diagnosis and treatment of various health conditions. The recent proliferation of data mining techniques has accelerated the development of disease prediction systems. In particular, machine learning methods are an effective way to analyze medical data and identify patterns to predict the likelihood of the disease development. Machine learning methods also help to identify biomarkers. Recently, the increasing incidence and mortality rates of inflammatory bowel disease, colorectal cancer and type 2 diabetes have drawn researchers' attention to these research areas. The aim of this thesis is to reduce the number of features and improve the prediction performance of machine learning based on complex biological datasets with a large number of disease-related features, as well as to identify potential biomarkers. In this thesis, three different studies are presented. The first study predicts eleven different cancer subgroups using miRNA data and biological domain knowledge and identifies potential biomarkers for these diseases. The second study predicts three different diseases using metagenomic data and biological domain knowledge and identifies potential biomarkers. The third study uses metagenomic data related to colorectal cancer to conduct global and population-based comprehensive experiments with traditional feature selection methods to identify potential biomarkers. This thesis presents a promising avenue for early disease detection, facilitating expedited treatment protocols, improving human survival rates, and potentially alleviating economic burdens within these critical research domains.
Citation - Scopus: 4
CCPred: Global and Population-Specific Colorectal Cancer Prediction and Metagenomic Biomarker Identification at Different Molecular Levels Using Machine Learning Techniques
(Elsevier Ltd, 2024) Bakir-Güngör, Burcu; Temiz, Mustafa; Inal, Yasin; Cicekyurt, Emre; Yousef, Malik
Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related deaths. Recent research highlights the pivotal role of the gut microbiota in CRC development and progression. Understanding the complex interplay between disease development and metagenomic data is essential for CRC diagnosis and treatment. Current computational models employ machine learning to identify metagenomic biomarkers associated with CRC, yet there is a need to improve their accuracy through a holistic biological knowledge perspective. This study aims to evaluate CRC-associated metagenomic data at species, enzymes, and pathway levels via conducting global and population-specific analyses. These analyses utilize relative abundance values from human gut microbiome sequencing data and robust classification models are built for disease prediction and biomarker identification. For global CRC prediction and biomarker identification, the features that are identified by SelectKBest (SKB), Information Gain (IG), and Extreme Gradient Boosting (XGBoost) methods are combined. Population-based analysis includes within-population, leave-one-dataset-out (LODO) and cross-population approaches. Four classification algorithms are employed for CRC classification. Random Forest achieved an AUC of 0.83 for species data, 0.78 for enzyme data and 0.76 for pathway data globally. On the global scale, potential taxonomic biomarkers include ruthenibacterium lactatiformanas; enzyme biomarkers include RNA 2′ 3′ cyclic 3′ phosphodiesterase; and pathway biomarkers include pyruvate fermentation to acetone pathway. This study underscores the potential of machine learning models trained on metagenomic data for improved disease prediction and biomarker discovery. The proposed model and associated files are available at https://github.com/TemizMus/CCPRED. © 2024 Elsevier B.V., All rights reserved.
Citation - WoS: 20
Citation - Scopus: 24
miRdisNET: Discovering MicroRNA Biomarkers That Are Associated With Diseases Utilizing Biological Knowledge-Based Machine Learning
(Frontiers Media S.A., 2023) Jabeer, Amhar; Temiz, Mustafa; Bakir-Gungor, Burcu; Yousef, Malik
During recent years, biological experiments and increasing evidence have shown that MicroRNAs play an important role in the diagnosis and treatment of human complex diseases. Therefore, to diagnose and treat human complex diseases, it is necessary to reveal the associations between a specific disease and related miRNAs. Although current computational models based on machine learning attempt to determine miRNA-disease associations, the accuracy of these models need to be improved, and candidate miRNA-disease relations need to be evaluated from a biological perspective. In this paper, we propose a computational model named miRdisNET to predict potential miRNA-disease associations. Specifically, miRdisNET requires two types of data, i.e., miRNA expression profiles and known disease-miRNA associations as input files. First, we generate subsets of specific diseases by applying the grouping component. These subsets contain miRNA expressions with class labels associated with each specific disease. Then, we assign an importance score to each group by using a machine learning method for classification. Finally, we apply a modeling component and obtain outputs. One of the most important outputs of miRdisNET is the performance of miRNA-disease prediction. Compared with the existing methods, miRdisNET obtained the highest AUC value of .9998. Another output of miRdisNET is a list of significant miRNAs for disease under study. The miRNAs identified by miRdisNET are validated via referring to the gold-standard databases which hold information on experimentally verified MicroRNA-disease associations. miRdisNET has been developed to predict candidate miRNAs for new diseases, where miRNA-disease relation is not yet known. In addition, miRdisNET presents candidate disease-disease associations based on shared miRNA knowledge. The miRdisNET tool and other supplementary files are publicly available at: .
Citation - Scopus: 1
Semant - Feature Group Selection Utilizing Fasttext-Based Semantic Word Grouping, Scoring, and Modeling Approach for Text Classification
(Springer International Publishing AG, 2024) Voskergian, Daniel; Bakir-Gungor, Burcu; Yousef, Malik
Text classification presents a challenge due to its high-dimensional feature space. As such, devising an effective feature selection scheme is essential. In this study, we present SEMANT, a novel hybrid filter-wrapper feature selection method that utilizes filter-based Chi-Square and the wrapper-based G-S-M approach. SEMANT incorporates fastText neural word embedding similarities to promote greater semantic inclusion in the selection of features for text classification tasks. The performance of the proposed method was investigated on the WOS-5736 and LitCovid datasets and compared with TextNetTopics, a topic modeling-based topic selection algorithm for text classification. Experimental results confirm that the proposed approach outperforms its alternative.
Machine Learning-Based Prediction of Autism Spectrum Disorder and Discovery of Related Metagenomic Biomarkers With Explainable AI
(MDPI, 2025) Temiz, Mustafa; Bakir-Gungor, Burcu; Ersoz, Nur Sebnem; Yousef, Malik
Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Recent studies have suggested that gut microbiota may play a role in the pathophysiology of ASD. This study aims to develop a classification model for ASD diagnosis and to identify ASD-associated biomarkers by analyzing metagenomic data at the taxonomic level. Methods: The performances of five different methods were tested in this study. These methods are (i) SVM-RCE, (ii) RCE-IFE, (iii) microBiomeGSM, (iv) different feature selection methods, and (v) a union method. The last method is based on creating a union feature set consisting of the features with importance scores greater than 0.5, identified using the best-performing feature selection methods. Results: In our 10-fold Monte Carlo cross-validation experiments on ASD-associated metagenomic data, the most effective performance metric (an AUC of 0.99) was obtained using the union feature set (17 features) and the AdaBoost classifier. In other words, we achieve superior machine learning performance with a few features. Additionally, the SHAP method, which is an explainable artificial intelligence method, is applied to the union feature set, and Prevotella sp. 109 is identified as the most important microorganism for ASD development. Conclusions: These findings suggest that the proposed method may be a promising approach for uncovering microbial patterns associated with ASD and may inform future research in this area. This study should be regarded as exploratory, based on preliminary findings and hypothesis generation.
Citation - Scopus: 2
Prediction 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) Bakir-Güngör, Burcu; Temiz, Mustafa; Canakcimaksutoglu, Beyza; Yousef, Malik
Colorectal 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.
Citation - Scopus: 25
Recursive Cluster Elimination Based Rank Function (SVM-RCE-R) Implemented in KNIME
(F1000 Research Ltd, 2021) Yousef, Malik; Bakir-Güngör, Burcu; Jabeer, Amhar; Göy, Gökhan; Qureshi, Rehman A.; 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.
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) 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: 52
Citation - Scopus: 63
Application of Biological Domain Knowledge Based Feature Selection on Gene Expression Data
(MDPI, 2021) Yousef, Malik; Kumar, Abhishek; Bakir-Gungor, Burcu
In the last two decades, there have been massive advancements in high throughput technologies, which resulted in the exponential growth of public repositories of gene expression datasets for various phenotypes. It is possible to unravel biomarkers by comparing the gene expression levels under different conditions, such as disease vs. control, treated vs. not treated, drug A vs. drug B, etc. This problem refers to a well-studied problem in the machine learning domain, i.e., the feature selection problem. In biological data analysis, most of the computational feature selection methodologies were taken from other fields, without considering the nature of the biological data. Thus, integrative approaches that utilize the biological knowledge while performing feature selection are necessary for this kind of data. The main idea behind the integrative gene selection process is to generate a ranked list of genes considering both the statistical metrics that are applied to the gene expression data, and the biological background information which is provided as external datasets. One of the main goals of this review is to explore the existing methods that integrate different types of information in order to improve the identification of the biomolecular signatures of diseases and the discovery of new potential targets for treatment. These integrative approaches are expected to aid the prediction, diagnosis, and treatment of diseases, as well as to enlighten us on disease state dynamics, mechanisms of their onset and progression. The integration of various types of biological information will necessitate the development of novel techniques for integration and data analysis. Another aim of this review is to boost the bioinformatics community to develop new approaches for searching and determining significant groups/clusters of features based on one or more biological grouping functions.
Leveraging MicroRNA-Gene Associations With Mirgedinet: An Intelligent Approach for Enhanced Classification of Breast Cancer Molecular Subtypes
(Springer International Publishing AG, 2025) Qumsiyeh, Emma; Bakir-Gungor, Burcu; Yousef, Malik
Understanding the molecular subtypes of breast cancer is crucial for advancing targeted therapies and precision medicine. For the BRCA molecular subtype prediction problem, this study employs miRGediNET, a machinelearning approach that integrates data from miRTarBase, DisGeNET, and HMDD databases to investigate shared gene associations between microRNA (miRNA) activity and disease mechanisms. Using the BRCA LumAB_Her2Basal dataset, we evaluate miRGediNET's performance against traditional feature selection methods, including CMIM, mRmR, Information Gain (IG), SelectKBest (SKB), Fast Correlation-Based Filter (FCBF), and XGBoost (XGB). These feature selection techniques were assessed using various classification algorithms including Random Forest (RF), Support Vector Machine (SVM), LogitBoost, Decision Tree, and AdaBoost, all executed with default parameters. The feature selection methods were tested using Monte Carlo Cross-Validation, where performance metrics obtained for each iteration were averaged to ensure robustness. Our findings reveal that miRGediNET outperforms traditional methods in accuracy and Area Under the Curve (AUC), emphasizing its superior capability to identify key genes that bridge miRNA interactions and breast cancer mechanisms. Notably, both miRGediNET and Information Gain (IG) feature selection consistently identified ESR1, a critical biomarker frequently reported in recent research associated with breast cancer prognosis and resistance to endocrine therapies. This integrative approach provides deeper biological insights into miRNA-disease interactions, paving the way for enhanced patient stratification, biomarker discovery, and personalized medicine strategies. The miRGediNET tool, developed on the KNIME platform, offers a practical resource for further exploration in the field of bioinformatics and oncology.
Citation - Scopus: 1
Engineering Novel Features for Diabetes Complication Prediction Using Synthetic Electronic Health Records
(Frontiers Media S.A., 2025) Voskergian, Daniel; Bakir-Gungor, Burcu; Yousef, Malik
Diabetes significantly affects millions of people worldwide, leading to substantial morbidity, disability, and mortality rates. Predicting diabetes-related complications from health records is crucial for early prevention and for the development of effective treatment plans. In order to predict four different complications of diabetes mellitus, i.e., retinopathy, chronic kidney disease, ischemic heart disease, and amputations, this study introduces a novel feature engineering approach. While developing the classification models, we utilize XGBoost feature selection method and various supervised machine learning algorithms, including Random Forest, XGBoost, LogitBoost, AdaBoost, and Decision Tree. These models were trained on synthetic electronic health records (EHR) generated by dual-adversarial autoencoders. These EHRs represent nearly 1 million synthetic patients derived from an authentic cohort of 979,308 individuals with diabetes. The variables considered in the models were the age range accompanied by chronic diseases that occur during patient visits starting from the onset of diabetes. Throughout the experiments, XGBoost and Random Forest demonstrated the best overall prediction performance. The final models, which are tailored to each complication and trained using our feature engineering approach, achieved an accuracy between 69% and 77% and an AUC between 77% and 84% using cross-validation, while the partitioned validation approach yielded an accuracy between 59% and 78% and an AUC between 66% and 85%. These findings imply that the performance of our method surpass the performance of the traditional Bag-of-Features approach, highlighting the effectiveness of our approach in enhancing model accuracy and robustness.
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) 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.
Citation - WoS: 1
Citation - Scopus: 2
RCE-IFE: Recursive Cluster Elimination With Intra-Cluster Feature Elimination
(PeerJ Inc, 2025) 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: 33
Citation - Scopus: 39
Inflammatory Bowel Disease Biomarkers of Human Gut Microbiota Selected via Different Feature Selection Methods
(PeerJ Inc, 2022) Bakir-Gungor, Burcu; Lar, Hilal Hac; Jabeer, Amhar; Nalbantoglu, Ozkan Ufuk; Aran, Oya; Yousef, Malik
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.
Population Specific Classification of Colorectal Cancer With Meta-Analysis of Metagenomic Data
(Institute of Electrical and Electronics Engineers Inc., 2023) Temiz, Mustafa; Yousef, Malik; Bakir-Güngör, Burcu
Advances in next-generation sequencing and '-omics' technologies makes it possible to characterize the human gut microbiome. While some of these microorganisms are important regulators of our immune system, modulation of the microbiota leads to a variety of diseases. Colorectal cancer (CRC), the third most common cancer worldwide, is caused by genetic mutations, environmental conditions, and abnormalities in the gut microbiota. Using various machine learning methods and meta-analysis techniques, this study aims to build a classification model that can help in CRC diagnosis by analyzing metagenomic datasets of different populations obtained at the species level. Using 8 different countries and 9 different metagenomic datasets, 3 different meta-analyzes are performed: within-population, cross-population, and one population is selected for testing and the rest is used as a training dataset (LODO). For CRC classification, 4 different classification algorithms (Random Forest (RF), Logitboost, Adaboost, and Decision Tree (DT)) are used. The best performance among these methods was obtained with the Random Forest algorithm with an AUC of 0.98 by using JP for the training data set and JPN populations for the test data set in the cross-population performance evaluation. © 2023 Elsevier B.V., All rights reserved.
Citation - WoS: 20
Citation - Scopus: 26
Prediction of Linear Cationic Antimicrobial Peptides Active Against Gram-Negative and Gram-Positive Bacteria Based on Machine Learning Models
(MDPI, 2022) Soylemez, Ummu Gulsum; Yousef, Malik; Kesmen, Zulal; Buyukkiraz, Mine Erdem; Bakir-Gungor, Burcu
Antimicrobial peptides (AMPs) are considered as promising alternatives to conventional antibiotics in order to overcome the growing problems of antibiotic resistance. Computational prediction approaches receive an increasing interest to identify and design the best candidate AMPs prior to the in vitro tests. In this study, we focused on the linear cationic peptides with non-hemolytic activity, which are downloaded from the Database of Antimicrobial Activity and Structure of Peptides (DBAASP). Referring to the MIC (Minimum inhibition concentration) values, we have assigned a positive label to a peptide if it shows antimicrobial activity; otherwise, the peptide is labeled as negative. Here, we focused on the peptides showing antimicrobial activity against Gram-negative and against Gram-positive bacteria separately, and we created two datasets accordingly. Ten different physico-chemical properties of the peptides are calculated and used as features in our study. Following data exploration and data preprocessing steps, a variety of classification algorithms are used with 100-fold Monte Carlo Cross-Validation to build models and to predict the antimicrobial activity of the peptides. Among the generated models, Random Forest has resulted in the best performance metrics for both Gram-negative dataset (Accuracy: 0.98, Recall: 0.99, Specificity: 0.97, Precision: 0.97, AUC: 0.99, F1: 0.98) and Gram-positive dataset (Accuracy: 0.95, Recall: 0.95, Specificity: 0.95, Precision: 0.90, AUC: 0.97, F1: 0.92) after outlier elimination is applied. This prediction approach might be useful to evaluate the antibacterial potential of a candidate peptide sequence before moving to the experimental studies.
Citation - Scopus: 5
Identifying Taxonomic Biomarkers of Colorectal Cancer in Human Intestinal Microbiota Using Multiple Feature Selection Methods
(Institute of Electrical and Electronics Engineers Inc., 2022) Jabeer, Amhar; Kocak, Aysegul; Akkaş, Huseyin; Yenisert, Ferhan; Nalbantoĝlu, Özkan Ufuk; Yousef, Malik; Bakir-Güngör, Burcu
A 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.
Citation - WoS: 25
Citation - Scopus: 31
miRmoduleNet: Detecting miRNA-mRNA Regulatory Modules
(Frontiers Media S.A., 2022) 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: 1
Citation - Scopus: 1
Prediction of Type 2 Diabetes Using Metagenomic Data and Identification of Taxonomic Biomarkers
(IEEE, 2024) Temiz, Mustafa; Kuzudisli, Cihan; Yousef, Malik; Bakir-Gungor, Burcu
Nowadays, different molecular levels of -omics data on diseases are generated and analyzing these data with machine learning methods is one of the popular research topics. Among these data, the use of metagenomic data to facilitate the diagnosis, detection and treatment of diseases is increasing day by day. Type 2 diabetes (T2D) is a chronic disease characterized by insulin resistance and progressive dysfunction of pancreatic beta cells. While the number of people with diabetes is increasing by around 8% annually, the cost of treating the disease is rising by 18% per year. Therefore, the number of studies on the diagnosis, development and progression of T2D is increasing over time. The aim of this study is to achieve higher machine learning performance by using fewer metagenomic features and to achieve better classification performance by reducing computational costs. In this study, we compare the performance of three different methods using T2D-related metagenomic data. First, the MetaPhlAn tool is used to calculate the taxonomic species and their relative abundances in each sample. The SVM-RCE, RCE-IFE and microBiomeGSM tools used in this study are methods that perform classification by grouping and scoring features and are known to work well on complex datasets. In this study, the best results were obtained with the RCE-IFE tool with an AUC of 0.72 with an average of 125 features information. In addition, key taxonomic species identified by these tools as associated with T2D are presented in comparison to the literature.
Citation - WoS: 16
Citation - Scopus: 20
GeNetOntology: 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) Ersoz, Nur Sebnem; Bakir-Gungor, Burcu; Yousef, Malik
Introduction: 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.