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.Conference Object Citation - WoS: 2Citation - Scopus: 2Classification of Breast Cancer Molecular Subtypes With Grouping-Scoring Approach That Incorporates Disease-Disease Association Information(IEEE, 2024-05-15) Qumsiyeh, Emma; Bakir-Gungor, Burcu; Yousef, MalikThis study uses modern sequencing technology and large biological databases to investigate the molecular intricacies of complicated diseases like cancer. Using gene expression databases and biomarkers, the research aims to improve breast cancer molecular subtype identification for better patient outcomes. Using BRCA LumAB_ Her2Basal dataset, this study compares an integrative machine learning-based strategy (GediNET) to traditional feature selection approaches across machine learning classifiers. GediNET excels at uncovering crucial disease-disease connections and potential biomarkers using the Grouping-Scoring-Modeling (GSM) approach, which favors gene groupings above individual genes. Our comparative analysis highlights GediNET's exceptional performance, notably in terms of accuracy and Area Under the Curve metrics, underscoring its effectiveness in uncovering the genetic intricacies of breast cancer. GediNET's promise to improve disease classification and biomarker identification by improving biological mechanism understanding goes beyond exceeding traditional approaches. The work shows that GediNET's integrative method can promote bioinformatics research by identifying the most informative genes associated with certain diseases, enabling focused and customized medicine.