Scopus İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395

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  • Article
    Citation - WoS: 26
    Citation - Scopus: 31
    miRcorrNet: Machine Learning-Based Integration of miRNA and mRNA Expression Profiles, Combined with Feature Grouping and Ranking
    (PeerJ Inc., 2021-05-19) Yousef, M.; Göy, G.; Mitra, R.; Eischen, C.M.; Jabeer, A.; Bakir-Güngör, B.
    A better understanding of disease development and progression mechanisms at the molecular level is critical both for the diagnosis of a disease and for the development of therapeutic approaches. The advancements in high throughput technologies allowed to generate mRNA and microRNA (miRNA) expression profiles; and the integrative analysis of these profiles allowed to uncover the functional effects of RNA expression in complex diseases, such as cancer. Several researches attempt to integrate miRNA and mRNA expression profiles using statistical methods such as Pearson correlation, and then combine it with enrichment analysis. In this study, we developed a novel tool called miRcorrNet, which performs machine learning-based integration to analyze miRNA and mRNA gene expression profiles. miRcorrNet groups mRNAs based on their correlation to miRNA expression levels and hence it generates groups of target genes associated with each miRNA. Then, these groups are subject to a rank function for classification. We have evaluated our tool using miRNA and mRNA expression profiling data downloaded from The Cancer Genome Atlas (TCGA), and performed comparative evaluation with existing tools. In our experiments we show that miRcorrNet performs as good as other tools in terms of accuracy (reaching more than 95% AUC value). Additionally, miRcorrNet includes ranking steps to separate two classes, namely case and control, which is not available in other tools. We have also evaluated the performance of miRcorrNet using a completely independent dataset. Moreover, we conducted a comprehensive literature search to explore the biological functions of the identified miRNAs. We have validated our significantly identified miRNA groups against known databases, which yielded about 90% accuracy. Our results suggest that miRcorrNet is able to accurately prioritize pan-cancer regulating high-confidence miRNAs. miRcorrNet tool and all other supplementary files are available at https://github.com/ malikyousef/miRcorrNet. © 2021 Elsevier B.V., All rights reserved.
  • Article
    Topological Feature Generation for Link Prediction in Biological Networks
    (PeerJ Inc, 2023-05-09) Temiz, Mustafa; Bakir-Gungor, Burcu; Sahan, Pinar Guner; Coskun, Mustafa; Güner Şahan, Pınar
    Graph or network embedding is a powerful method for extracting missing or potential information from interactions between nodes in biological networks. Graph embedding methods learn representations of nodes and interactions in a graph with low-dimensional vectors, which facilitates research to predict potential interactions in networks. However, most graph embedding methods suffer from high computational costs in the form of high computational complexity of the embedding methods and learning times of the classifier, as well as the high dimensionality of complex biological networks. To address these challenges, in this study, we use the Chopper algorithm as an alternative approach to graph embedding, which accelerates the iterative processes and thus reduces the running time of the iterative algorithms for three different (nervous system, blood, heart) undirected protein-protein interaction (PPI) networks. Due to the high dimensionality of the matrix obtained after the embedding process, the data are transformed into a smaller representation by applying feature regularization techniques. We evaluated the performance of the proposed method by comparing it with state-of-the-art methods. Extensive experiments demonstrate that the proposed approach reduces the learning time of the classifier and performs better in link prediction. We have also shown that the proposed embedding method is faster than state-of-the-art methods on three different PPI datasets.
  • Article
    Thermal Stresses in SOFC Stacks: The Role of Mismatch Among Thermal Conductivity of Adjacent Components
    (Tubitak Scientific & Technological Research Council Turkey, 2021-06-30) Aydin, Ozgur; Matsumoto, Go; Shiratori, Yusuke
    Generating power from renewable biogas in solid oxide fuel cells (SOFCs) is an environment-friendly, efficient, and promising energy conversion process. Biogas can be used in SOFCs via a reforming process for which dry reforming is more suitable as the reforming agent exists in the biogas mixture. Biogas can be directly reformed to H-2 -rich fuel stream in the anode chamber of a SOFC by the heat released during power generation. Exploiting the heat and water produced in the SOFC for internal reforming of biogas makes the energy conversion process very efficient; however, various challenges are reported. Thus, indirect internal reforming is opted for which a separate reforming domain is required. In an indirect internal reformer operating at usual conditions, dry reforming rate is quite high in the inlet and it decreases steeply toward the fuel outlet. Great temperature gradients develop over the reformer, since the dry reforming reaction is strongly endothermic. The abruptly varying rate of the reforming reaction affects the temperature fields in the adjacent components of SOFC and hence intolerable thermal stresses emerge on the SOFC components. In our preceding study, we graded the reforming domain, homogenized the temperature profile over the reforming domain, and executed performance and durability experiments. However, most of the experiments failed due to fracturing SOFC components hinting at existence of thermal stresses. In that study, we focused on minimizing the temperature gradients within the reforming domain; namely, we neglected the other processes. To eliminate the thermal stresses, we modeled the entire module of SOFC equipped with a reformer featuring a graded reforming domain. We found that the mismatch between the thermal conductivities of the adjacent module components is the major reason for the thermal stresses. When the mismatch is eliminated, thermal stresses disappear even if the reforming domain is not graded.
  • Article
    Citation - WoS: 6
    Citation - Scopus: 7
    Therapeutic Potential of Nitrogen-Substituted Oleanolic Acid Derivatives in Neuroinflammatory and Cytokine Pathways: Insights From Cell-Based and Computational Models
    (Wiley-VCH Verlag GmbH, 2025-04-22) Turgut, Gurbet Celik; Pepe, Nihan Aktas; Ekiz, Yagmur Ceylan; Senol, Halil; Sen, Alaattin
    This study was conducted to investigate the mechanism of the potential and anti-inflammatory properties of nitrogen-substituted oleanolic acid derivatives that can be used to treat neuroinflammatory diseases. Nitrogen-containing oleanolic acid derivatives have been evaluated for their anti-neuroinflammatory effects in vitro in neuronal and monocytic cell lines at nontoxic doses, and the production of cytokines (TNF-alpha, IL-6 and IL-17), the inflammatory enzyme induced nitric oxide synthase (iNOS) and NF-kappa B signalling under LPS-stimulated conditions, and the expression of genes associated with Alzheimer's disease have been assessed. In addition, molecular docking and molecular dynamics simulation assessments are conducted in silico. Key protein markers of neurodegenerative diseases, especially Alzheimer's disease and neuroinflammation, TAU protein levels, and microglial activation, as well as ionised calcium-binding adaptor protein-1 (IBA1) levels, were significantly reduced with the addition of oleanolic acid derivatives. LPS-induced NF-kappa B luciferase reporter activity and iNOS activity were significantly inhibited, approaching the levels in uninduced controls. The mRNA expression of proinflammatory cytokines critical for neuroinflammation, such as TNF-alpha, NF-kappa B, IL-6 and IL-17, was reduced twofold to sevenfold. Furthermore, the molecular docking and MD simulation analyses revealed potential interactions with the TNF-alpha and NF-kappa B proteins. These findings underscore the potential of oleanolic acid derivatives, particularly compound 16, as candidates for further development as therapeutic agents for neurodegenerative diseases associated with chronic inflammation.
  • Article
    Theoretical Investigation of Steric Effects on the S1 Potential Energy Surface of O-Carborane Derivatives
    (Tubitak Scientific & Technological Research Council Turkey, 2023-01-01) Alkan, Fahri
    TDDFT scan calculations were performed for s-carborane-anthracene derivatives (o-CB-X-Ant where X=-H,-CH3,-C2H5 and tert-butyl or-tBu) in order to understand the interplay between the steric effects, S1 potential energy surface (PES) and photophysical properties. The results show that all systems exhibit three local minima on the S1 PES, which correspond to the emissive LE and TICT state, along with the nonemissive CT state respectively. In the case of the unsubstituted system (o-CB-H-Ant), and-CH3 and-C2H5 substituted cases, S1 PES is predicted to be quite flat for certain conformations indicating that it is possible for these systems to reach the nonemissive CT state without a large energy penalty. In comparison, conformational pathways for the nonemissive CT state are predicted to be energetically unfavorable for o-CB-tBu-Ant as a result of both steric and electronic effects. These results provide a mechanism for the enhanced emission of cr-CB-fluorophore molecules with bulky ligands.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Theoretical Investigation of Substituent Effects on the Relative Stabilities and Electronic Structure of [BnXn]2- Clusters
    (Springer, 2021-11-29) Tahaoglu, Duygu; Alkan, Fahri; Durandurdu, Murat
    In this study, we provide a theoretical evaluation of relative stabilities and electronic structure for [BnXn](2-) clusters (n = 10, 12, 13, 14, 15, 16). Structural and electronic characteristics of [BnXn](2-) clusters are examined by comparison with the [B12X12](2-) counterparts with a focus on the substituent effects (X = H, F, Cl, Br, CN, BO, OH, NH2) on the electronic structure, electron detachment energies, formation enthalpies, and charge distributions. For the electronic structure and electron detachment energies, substituent effects on boron clusters are shown to follow a very similar trend to the mesomeric and inductive effects (+/- M and +/- I) of pi-conjugated systems, and the most stable derivatives in terms of HOMO/LUMO and electron detachment energies are calculated for CN and BO substituents due to strong -M effects. In the case of formation enthalpies for larger boron clusters (n >= 13), the icosahedral barrier is shown to increase with the halogen and CN substitution, whereas it is possible to reduce the icosahedral barrier for the cases of X = OH and NH2. It is shown that this reduction results from destabilizing the [B12X12](2-) cluster with electronic (+ M) and symmetry effects induced by OH and NH2 ligands.
  • Article
    Citation - WoS: 43
    Citation - Scopus: 49
    The Pleiotropic Effects of Fisetin and Hesperetin on Human Acute Promyelocytic Leukemia Cells Are Mediated Through Apoptosis, Cell Cycle Arrest, and Alterations in Signaling Networks
    (Sage Publications Ltd, 2015-06-17) Adan, Aysun; Baran, Yusuf
    Fisetin and hesperetin, flavonoids from various plants, have several pharmaceutical activities including antioxidative, anti-inflammatory, and anticancer effects. However, studies elucidating the role and the mechanism(s) of action of fisetin and hesperetin in acute promyelocytic leukemia are absent. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by fisetin and hesperetin on human HL60 acute promyelocytic leukemia cells. The viability of HL60 cells was evaluated using the MTT assay, apoptosis by annexin V/propidium iodide (PI) staining and cell cycle distribution using flow cytometry, and changes in caspase-3 enzyme activity and mitochondrial transmembrane potential. Moreover, we performed whole-genome microarray gene expression analysis to reveal genes affected by fisetin and hesperetin that can be important for developing of future targeted therapy. Based on data obtained from microarray analysis, we also described biological networks modulated after fisetin and hesperetin treatment by KEGG and IPA analysis. Fisetin and hesperetin treatment showed a concentration- and time-dependent inhibition of proliferation and induced G2/M arrest for both agents and G0/G1 arrest for hesperetin at only the highest concentrations. There was a disruption of mitochondrial membrane potential together with increased caspase-3 activity. Furthermore, fisetin- and hesperetin-triggered apoptosis was confirmed by annexin V/PI analysis. The microarray gene profiling analysis revealed some important biological pathways including mitogen-activated protein kinases (MAPK) and inhibitor of DNA binding (ID) signaling pathways altered by fisetin and hesperetin treatment as well as gave a list of genes modulated a parts per thousand yen2-fold involved in cell proliferation, cell division, and apoptosis. Altogether, data suggested that fisetin and hesperetin have anticancer properties and deserve further investigation.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    The Impact of COVID-19 on Healthcare Utilization in Turkey
    (Elsevier, 2024-09) Ugur, Zeynep B.; Durak, Aysenur
    Objectives: This study investigates the impact of the COVID-19 pandemic on healthcare utilization in Turkey. Methods: We utilized individual-level data derived from Turkish Statistical Institute 's annual surveys between 2014 and 2022 and estimated probit regression models. Results: We find that COVID-19 pandemic reduced healthcare utilization by 11.8% after taking into account a large set of background variables. Although our study finds that the elderly and those with health problems are more likely to use healthcare services under normal circumstances, the COVID-19 pandemic has caused notable drops in the healthcare utilization among the elderly (-6.5%) and those with health problems (-3.8%). Although those without health insurance had lower utilization of healthcare services before the pandemic, during the pandemic they were not particularly hit. Conclusion: We conclude that the pandemic did not lower the healthcare utilization in Turkey because of the supply constraints. Also, the evidence points to the reduced demand due to the fear of contagion rather than financial concerns.
  • Article
    Citation - WoS: 9
    Citation - Scopus: 13
    The Impact and Future of Artificial Intelligence in Medical Genetics and Molecular Medicine: An Ongoing Revolution
    (Springer Heidelberg, 2024-08) Ozcelik, Firat; Dundar, Mehmet Sait; Yildirim, A. Baki; Henehan, Gary; Vicente, Oscar; Sanchez-Alcazar, Jose A.; Dundar, Munis
    Artificial intelligence (AI) platforms have emerged as pivotal tools in genetics and molecular medicine, as in many other fields. The growth in patient data, identification of new diseases and phenotypes, discovery of new intracellular pathways, availability of greater sets of omics data, and the need to continuously analyse them have led to the development of new AI platforms. AI continues to weave its way into the fabric of genetics with the potential to unlock new discoveries and enhance patient care. This technology is setting the stage for breakthroughs across various domains, including dysmorphology, rare hereditary diseases, cancers, clinical microbiomics, the investigation of zoonotic diseases, omics studies in all medical disciplines. AI's role in facilitating a deeper understanding of these areas heralds a new era of personalised medicine, where treatments and diagnoses are tailored to the individual's molecular features, offering a more precise approach to combating genetic or acquired disorders. The significance of these AI platforms is growing as they assist healthcare professionals in the diagnostic and treatment processes, marking a pivotal shift towards more informed, efficient, and effective medical practice. In this review, we will explore the range of AI tools available and show how they have become vital in various sectors of genomic research supporting clinical decisions.
  • Article
    Citation - WoS: 15
    Citation - Scopus: 11
    T Cells in Tumor Microenvironment
    (Springer, 2015-10-18) Kiraz, Yagmur; Baran, Yusuf; Nalbant, Ayten
    Tumors progress in a specific area, which supports its development, spreading or shrinking in time with the presence of different factors that effect the fate of the cancer cells. This specialized site is called "tumor microenvironment" and has a composition of heterogenous materials. The immune cells are also residents of this stromal, cancerous, and inflammatory environment, and their types, densities, or functional differences are one of the key factors that mediate the fate of a tumor. T cells as a vital part of the immune system also are a component of tumor microenvironment, and their roles have been elucidated in many studies. In this review, we focused on the immune system components by focusing on T cells and detailed T helper cell subsets in tumor microenvironment and how their behaviors affect either the tumor or the patient's outcome.