Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article TEffectBayes: A Nextflow Pipeline for Exploring the Potential Effect of Transposable Elements in Gene Regulatory Network with Multi-Omic Bayesian Network Model(Springer Heidelberg, 2026-03-10) Karakülah, Gökhan; Güner, Hüseyin; Kutlu, Necati KaanTransposable elements (TEs) are critical contributors to gene regulatory networks, yet their repetitive and abundant nature complicates efforts to elucidate their precise regulatory roles. While existing computational tools facilitate systematic identification of associations between TEs and gene expression, these methods typically cannot account for confounding variables or capture causal and directional interactions. To address these limitations, we developed TEffectBayes, a Nextflow-based pipeline leveraging a multi-omic Bayesian network (BN) framework designed to systematically infer directional, probabilistic regulatory dependencies involving TEs. TEffectBayes integrates diverse omics datasets, including RNA-seq-derived gene and locus-specific TE expression, along with ChIP-seq-based histone modification data processed via custom R and Python scripts. Integrated multi-omic datasets are subsequently employed to build gene-centric Bayesian models, enabling robust inference of context-dependent, probabilistic relationships between TEs, chromatin modifications, and gene expression. TEffectBayes thus provides a reproducible and scalable computational framework for unraveling the complex regulatory landscape shaped by TEs. In summary, TEffectBayes supports systematic prioritization of TE-chromatin-gene regulatory candidates for downstream benchmarking and experimental validation, enabling hypothesis-driven follow-up studies in diverse biological contexts. The pipeline, along with comprehensive user tutorials and example datasets, is publicly accessible at https://github.com/nkaan-kutlu/TEffectBayes.Conference Object Impact of Gene Duplicate Handling Strategies on Classification Performance and Feature Selection in Gene Expression Data(Institute of Electrical and Electronics Engineers Inc., 2025-09-17) Kuzudisli, Cihan; Qaqish, Bahjat; Gungor, Burcu Bakir; Yousef, MalikArticle Citation - WoS: 4Citation - Scopus: 4Evaluation of Selected Plant Phenolics Via Beta-Secretase Inhibition, Molecular Docking, and Gene Expression Related to Alzheimer's Disease(MDPI, 2024-10-28) Akyurek, Tugba Ucar; Orhan, Ilkay Erdogan; Deniz, F. Sezer Senol; Eren, Gokcen; Acar, Busra; Sen, Alaattin; Şenol Deniz, F. Sezer; Uçar Akyürek, TugbaBackground: The goal of the current study was to investigate the inhibitory activity of six phenolic compounds, i.e., rosmarinic acid, gallic acid, oleuropein, epigallocatechin gallate (EGCG), 3-hydroxytyrosol, and quercetin, against beta-site amyloid precursor protein cleaving enzyme-1 (BACE1), also known as beta-secretase or memapsin 2, which is implicated in the pathogenesis of Alzheimer's disease (AD). Methods and Results: The inhibitory potential against BACE1, molecular docking simulations, as well as neurotoxicity and the effect on the AD-related gene expression of the selected phenolics were tested. BACE1 inhibitory activity was carried out using the ELISA microplate assay via fluorescence resonance energy transfer (FRET) technology. Molecular docking experiments were performed in the human BACE1 active site (PDB code: 2WJO). Neurotoxicity of the compounds was carried out in SH-SY5Y, a human neuroblastoma cell line, by the Alamar Blue method. A gene expression analysis of the compounds on fourteen genes linked to AD was conducted using the real-time polymerase chain reaction (RT-PCR) method. Rosmarinic acid, EGCG, oleuropein, and quercetin (also used as the reference) were able to inhibit BACE1 with their respective IC50 values 4.06 +/- 0.68, 1.62 +/- 0.12, 9.87 +/- 1.01, and 3.16 +/- 0.30 mM. The inhibitory compounds were observed to occupy the non-catalytic site of the BACE1. However, hydrogen bonds were found to be present between rosmarinic acid and EGCG and aspartic amino acid D228 in the catalytic site. Oleuropein and quercetin effectively suppressed the expression of PSEN, APOE, and CLU, which are recognized to be linked to the pathogenesis of AD. Conclusions: The outcomes of the work bring quercetin, EGCG, and rosmarinic acid to the forefront as promising BACE1 inhibitors.Conference Object Hepatoselüler Karsinom Oluşumunda Etkili Moleküler Mekanizmaların İn Siliko Yöntemlerle Araştırılması(Institute of Electrical and Electronics Engineers Inc., 2020-09) Doǧan, Refika Sultan; Saka, Samed; Bakir-Güngör, Burcu; Gungor, Burcu BakirHepatocellular carcinoma (HCC) is the most common cause of cancer-related death in the world. The molecular changes in the organism during the development of HCC are not fully understood. The aim of the present study is to contribute to the identification of critical genes and pathways associated with HCC via integrating various bioinformatics methods. In this study, experiments were conducted on gene expression data of 14 HCC tissues and noncancerous control tissues. A total of 1229 genes, which show a statistically significant change between the groups, were identified. Among these, 681 genes were upregulated and 548 genes were downregulated. Via mapping the detected genes into protein protein interaction networks, active subnetwork search, subnetwork topological analysis and functional enrichment analyses were carried out. The interactions between the molecular pathways affected by HCC were also presented. © 2020 Elsevier B.V., All rights reserved.Conference Object Nöromüsküler Hastalıkların Ortak MikroRNA ve Yolaklarının İn Siliko Yöntemlerle Belirlenmesi(Institute of Electrical and Electronics Engineers Inc., 2019-04) Ünlü Yazici, Miray; Aksu-Menges, Evrim; Akkaya-Ulum, Yeliz Z.; Balcihayta, Burcu; Bakir-Güngör, BurcuNeuromuscular disorders (NMD) are a heterogeneous group of diseases characterized by the loss of function of the peripheral nerves and muscles. However, there are no effective and widespread therapeutic approaches to prevent or delay the progression of these disease types. MicroRNAs (miRNAs) which cause significant changes in gene expression by binding to target messenger RNAs (mRNAs), are known to have an effect on disease mechanisms. In this study, by integrating different bioinformatics methods, we aim to find miRNAs, target genes and pathways related to a group of neuromuscular diseases. For this purpose, we determined 17 miRNAs that show significant expression changes between patient and healthy groups; predicted target genes of these miRNAs; and identified affected pathways using subnetwork discovery, functional enrichment based algorithms. In our study, we integrated different in-silico approaches that proceed in topdown manner or bottom-up manner. The identified candidate miRNAs, genes and pathways, which could help to explain neuromuscular disease development mechanisms, are now under investigation in wet-lab. © 2020 Elsevier B.V., All rights reserved.Article Citation - Scopus: 3Combined Effect of Midostaurin and Sphingosine Kinase-1 İnhibitor on FMS-Like Tyrosine Kinase 3 (FLT3) Wild Type Acute Myeloid Leukemia Cells(De Gruyter Open Ltd, 2022) Şahin, Hande Nur; Adan, AysunObjectives: Therapeutic potential of clinically approved FLT3 inhibitor midostaurin has been neglected in wild-type FLT3 positive acute myeloid leukemia (AML). Sphingosine kinase-1 (SK-1) having anti-proliferative functions is studied in various cancers, but not in FLT3 wild-type AML. We aimed to develop new therapeutic strategies to combat FLT3 wild-type AML by combining midostaurin with SK-1 inhibitor (SKI II) in THP1 cells. Methods: The anti-proliferative effects of midostaurin, SKI II and in combination on THP1 cells were determined by MTT assay. The combination indexes were calculated using calcusyn software. SK-1 expression and PARP cleavage were checked by western blot. Cell cycle distributions (PI staining) and apoptosis (annexin-V/PI dual staining) were assessed by flow cytometry for each agent alone and in combinations. Results: Midostaurin decreased SK-1 protein level. Midostaurin, SKI II and certain combinations decreased cell viability in a dose dependent manner. The combined anti-leukemic effects of the aforementioned drug combination afforded additive effect. Co-administration induced both necrosis and apoptosis via phosphatidylserine externalization, PARP cleavage and cell cycle arrest at G0/G1 and S phases. Conclusions: Targeting sphingosine kinase-1 together with FLT3 inhibition could be a novel mechanism to increase limited clinic response to midostaurin in wild-type FLT3 overexpressing AML after further pre-clinical studies. © 2022 Elsevier B.V., All rights reserved.