PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Predicting Respiratory Infection and Symptoms Development Using Gene Set Enrichment Scores and Machine Learning(Elsevier Sci Ltd, 2026) Aydin, Zafer; Isik, Yunus EmreRecent advancements in precision medicine enable personalized predictions grounded in individual-level genetic data. However, relying solely on a single type of data can decrease prediction accuracy and limit the biological interpretability of the resulting models. Incorporating predefined genetic knowledge, such as derived gene sets, can improve performance and provide deeper biological insights for complex diseases, including respiratory infections. This study aimed to evaluate the usability of enrichment scores (ES), calculated using gene sets from the Molecular Signatures Database (MSigDB), as a feature representation for machine learning models to predict respiratory viral infections and symptom development. In addition, the proposed feature representation approach was extensively compared with the de facto gene-level expression representation. A total of 36,834 predefined gene sets were compiled from the MSigDB, and their ES values were calculated. Experiments used the GSE73072 dataset from Gene Expression Omnibus, containing gene expression profiles before and after virus exposure. Various machine learning and feature selection algorithms were applied to ES-based and probe-level feature sets. The results showed that both feature representation approaches achieved an area under the precision-recall curve (AUPRC) value greater than 0.90 for all tasks. Compared with the Respiratory Viral DREAM Challenge leaderboard phase, our models showed a 14.8% improvement in pre-exposure predictions (T0) and a 17.4% improvement in symptom classification. Using enrichment scores as a feature representation generally resulted in better performance than probe-level representation when predicting respiratory infections and symptom development. Identifying key gene sets through feature selection and comparing them with essential genes for respiratory viruses enabled a more comprehensive analysis, providing deeper insights into the pathways that contribute to these predictions.Article Functional Characterization of Loss of RNF43 Reveals Neuronal Defects in a Caenorhabditis Elegans Model(MDPI, 2026) Kazan, Hasan Huseyin; Turkyilmaz, Zafer; Ekim, Burcu; Kaya, Cem; Ergun, Mehmet Ali; Sonmez, Kaan; Güzel, SinemRing finger protein 43 (RNF43) encodes a transmembrane E3 ubiquitin ligase that negatively regulates canonical Wnt signaling and is classically associated with serrated polyposis syndrome and colorectal cancer. In this study, regarding a homozygous truncating RNF43 variant (NM_001305545.1:c.1906C>T; p.Gln636Ter) in a patient segregating with a severe neurodevelopmental phenotype characterized by developmental delay, neonatal hypotonia, recurrent seizures, progressive microcephaly, and bilateral optic atrophy, the loss of polarity defective 1 (plr-1), an ortholog of RNF43, was modeled in Caenorhabditis elegans and the phenotype was primarily characterized. The results demonstrated that loss of the plr-1 disrupted gamma aminobutyric acid (GABA)ergic axon organization, reduced locomotor speed calculated from 60 s recordings, and altered developmental growth. These findings expand the phenotypic spectrum of RNF43 and support a dosage-dependent developmental role.Article Citation - WoS: 5Citation - Scopus: 5Targeting Cholinergic Dysfunction and Neuroinflammation through Rationally Designed Thieno[3,2-d]Pyrimidine Hybrids(Academic Press Inc Elsevier Science, 2026-07) Acar, Ozden Ozgun; Acar, Busra; Senol, Halil; Tokali, Feyzi Sinan; Sen, Alaattin; Demir, Yeliz; Cakir, FurkanNeurodegenerative diseases involve the convergence of cholinergic dysfunction, neuronal loss, and sustained neuroinflammatory responses, necessitating the development of multifunctional therapeutic agents. In this study, a series of novel thieno[3,2-d]pyrimidine-phenolic Mannich base hybrids were rationally designed, synthesized, and evaluated as dual cholinesterase inhibitors with neuroprotective and anti-neuroinflammatory potential. The synthesized compounds exhibited potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with inhibition constants in the low nanomolar range. Among them, compounds 5 and 9 emerged as the most active derivatives, displaying Ki values of 8.79 and 14.11 nM for AChE and 7.04 and 11.75 nM for BChE, surpassing the reference inhibitors tacrine and donepezil. Molecular docking and molecular dynamics simulations supported the experimental findings, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations further confirmed their superior binding affinities compared with donepezil. Cytotoxicity profiling in SH-SY5Y neuronal cells and RAW 264.7 and THP-1 immune cells identified a narrow sub-cytotoxic concentration window (EC05-EC10 = 1.2-2.1 mu M), ensuring biological effects independent of nonspecific cell damage. Within this range, both compounds exerted pronounced antineuroinflammatory activity. Notably, compound 9 significantly downregulated pro-inflammatory mediators, reducing IL-1 beta, IL-6, and NF-kappa B1 gene expression by up to 2.78-, 3.37-, and 4.84-fold, respectively. Consistently, it suppressed nitric oxide production in LPS-stimulated macrophages to levels comparable with ascorbic acid and markedly decreased Iba1 expression in activated THP-1 cells. This integrated enzymatic, computational, and cellular investigation identifies compounds 5 and 9 as promising multifunctional lead combining dual cholinesterase inhibition with robust anti-neuroinflammatory activity. The results provide a strong foundation for future in vivo studies and further optimization toward disease-modifying agents for neurodegenerative disorders.Article Citation - Scopus: 5Integrated Querying and Version Control of Context-Specific Biological Networks(Oxford University Press, 2020-01-01) Coşkun, Mustafa; Grama, Ananth; Koyutürk, Mehmet; Cowman, TylerArticle Citation - WoS: 3Citation - Scopus: 3Two-Local Modifications of Sachdev-Ye Model With Quantum Chaos(American Physical Society, 2026-01-27) Hanada, M.; Van Leuven, S.; Oktay, O.; Tezuka, M.The Sachdev-Ye-Kitaev (SYK) model may provide us with a good starting point for the experimental study of quantum chaos and holography in the laboratory. Still, the four-local interaction of fermions makes quantum simulation challenging, and it would be good to search for simpler models that keep the essence. In this paper, we argue that the four-local interaction may not be important by introducing a few models that have two-local interactions. The first model is a generalization of the spin-SYK model, which is obtained by replacing the spin variables with SU(d) generators. Simulations of this class of models might be straightforward on qudit-based quantum devices. We study the case of d=3,4,5,6 numerically and observe quantum chaos already for two-local interactions in a wide energy range. We also introduce modifications of spin-SYK and SYK models that have similar structures as the SU(d) model (e.g., H=∑p,qJpqχpχp+1χqχq+1 instead of the original SYK Hamiltonian H=∑p,q,r,sJpqrsχpχqχrχs), which shows strongly chaotic features although the interaction is essentially two-local. These models may be a good starting point for the quantum simulation of the original SYK model. ©2026 American Physical Society.Article Citation - WoS: 2Citation - Scopus: 2Effect of Yttrium/Lanthanum-Doped Ultrasonically Assisted Nano-Hydroxyapatite on Remineralization and Bracket Bond Strength in Artificial Enamel Lesions(BMC, 2025-09-29) Ozturk, Taner; Mammadov, Elshan; Bulduk Karakaya, Humeyra; Yagci, Filiz; Dayan, Serkan; Yagci, AhmetBackground This in vitro study aimed to evaluate the remineralization efficacy of ultrasonically assisted yttrium fluoride-doped (Ult-YF3-nHAP) and lanthanum fluoride-doped (Ult-LaF3-nHAP) nano-hydroxyapatite (nHAP) on artificially induced enamel lesions (aWSLs), and to compare their performance with acidulated phosphate fluoride (APF) gel, fluoride varnish, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and resin infiltrant (ICON). Methods This in vitro study followed a four-phase design: enamel lesion creation, application of remineralization agents, a 14-day treatment protocol, and post-treatment analyses using QLF, Micro-CT, SEM-EDX, and SBS testing. This study included 168 extracted human premolars, divided into eight experimental groups (n = 21 per group): (1) Demineralized control (no remineralization treatment), (2) Acidulated phosphate fluoride (APF) gel, (3) Fluoride varnish, (4) Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), (5) Ultrasonically assisted nHAP (Control nHAP), (6) Ult-YF3-nHAP, (7) Ult-LaF3-nHAP, and (8) Resin infiltrant (ICON). The aWSLs were created under laboratory conditions. Brackets were bonded to the teeth with composite material, and aWSLs were created under laboratory conditions. After lesion formation and at the end of the experimental process, micro-computed tomography (Micro-CT) and laser-assisted quantitative light fluorescence (QLF) analysis were performed to assess lesion progression and remineralization. Additionally, scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and shear bond strength (SBS) tests were conducted at the end of the study. Statistical analysis was performed using one-way ANOVA, Kruskal-Wallis, and Mann-Whitney U tests, with a significance level of p < 0.05. Results The bracket bond strength test data showed no significant differences between the groups (p = 0.156). Significant differences were found among groups for QLF fluorescence recovery (Delta F, p < 0.001), with the Ult-YF3-nHAP group showing the greatest increase (median: +0.5, IQR: -1.4 to + 0.7), while the control group showed the greatest decrease (median: -12.1, IQR: -12.4 to -10.2). Micro-CT analysis also revealed significant differences between groups (p = 0.008). The APF Gel group showed values comparable to those of all other experimental groups. The highest remineralization values were recorded in the Ult-YF3-nHAP group (6.87 +/- 3.03 mm(3)), whereas the lowest values were found in the Varnish group. The demineralized control group had significantly higher values than the Varnish group, but lower than the Ult-LaF3-nHAP group. SEM-EDX analysis revealed that fluoride weight was significantly lower in the Tooth Mousse and Varnish groups compared to the other experimental groups (p < 0.001). Ca/P ratio was significantly lower in the demineralized control, Varnish, and Ult-YF3-nHAP groups than in other experimental groups (p = 0.002). Conclusion Ult-YF3-nHAP showed higher efficacy in remineralization of aWSLs compared to fluoride-based treatments, CPP-ACP, and resin infiltrant. The highest remineralization was detected in the Ult-YF3-nHAP group by micro-CT and QLF analysis, while fluoride varnish gave the lowest result.Article Citation - WoS: 13Citation - Scopus: 13Why Do Muse Stem Cells Present an Enduring Stress Capacity? Hints From a Comparative Proteome Analysis(MDPI, 2021-02-19) Acar, Mustafa B.; Aprile, Domenico; Ayaz-Guner, Serife; Guner, Huseyin; Tez, Coskun; Di Bernardo, Giovanni; Galderisi, UmbertoMuse cells are adult stem cells that are present in the stroma of several organs and possess an enduring capacity to cope with endogenous and exogenous genotoxic stress. In cell therapy, the peculiar biological properties of Muse cells render them a possible natural alternative to mesenchymal stromal cells (MSCs) or to in vitro-generated pluripotent stem cells (iPSCs). Indeed, some studies have proved that Muse cells can survive in adverse microenvironments, such as those present in damaged/injured tissues. We performed an evaluation of Muse cells' proteome under basic conditions and followed oxidative stress treatment in order to identify ontologies, pathways, and networks that can be related to their enduring stress capacity. We executed the same analysis on iPSCs and MSCs, as a comparison. The Muse cells are enriched in several ontologies and pathways, such as endosomal vacuolar trafficking related to stress response, ubiquitin and proteasome degradation, and reactive oxygen scavenging. In Muse cells, the protein-protein interacting network has two key nodes with a high connectivity degree and betweenness: NFKB and CRKL. The protein NFKB is an almost-ubiquitous transcription factor related to many biological processes and can also have a role in protecting cells from apoptosis during exposure to a variety of stressors. CRKL is an adaptor protein and constitutes an integral part of the stress-activated protein kinase (SAPK) pathway. The identified pathways and networks are all involved in the quality control of cell components and may explain the stress resistance of Muse cells.Article Citation - WoS: 7Citation - Scopus: 8The Determination of Distinctive Single Nucleotide Polymorphism Sets for the Diagnosis of Behcet's Disease(IEEE Computer Soc, 2022-05-01) Isik, Yunus Emre; Gormez, Yasin; Aydin, Zafer; Bakir-Gungor, BurcuBehcet's Disease (BD) is a multi-system inflammatory disorder in which the etiology remains unclear. The most probable hypothesis is that genetic tendency and environmental factors play roles in the development of BD. In order to find the essential reasons, genetic changes on thousands of genes should be analyzed. Besides, there is a need for extra analysis to find out which genetic factor affects the disease. Machine learning approaches have high potential for extracting the knowledge from genomics and selecting the representative Single Nucleotide Polymorphisms (SNPs) as the most effective features for the clinical diagnosis process. In this study, we have attempted to identify representative SNPs using feature selection methods, incorporating biological information and aimed to develop a machine-learning model for diagnosing Behcet's disease. By combining biological information and machine learning classifiers, up to 99.64 percent accuracy of disease prediction is achieved using only 13,611 out of 311,459 SNPs. In addition, we revealed the SNPs that are most distinctive by performing repeated feature selection in cross-validation experiments.Article Citation - Scopus: 25Synthesis and Comprehensive in Vivo Activity Profiling of Olean-12-en-28-ol, 3β-Pentacosanoate in Experimental Autoimmune Encephalomyelitis: A Natural Remyelinating and Anti-Inflammatory Agent(American Chemical Society, 2023-01-04) Şenol, Halil; Ozgun-Acar, Özden; Daǧ, Aydan; Eken, Ahmet; Guner, Hüseyin; Aykut, Zaliha Gamze; Sen, AlaattinMultiple sclerosis (MS) treatment has received much attention, yet there is still no certain cure. We herein investigate the therapeutic effect of olean-12-en-28-ol, 3β-pentacosanoate (OPCA) on a preclinical model of MS. First, OPCA was synthesized semisynthetically and characterized. Then, the mice with MOG<inf>35-55</inf>-induced experimental autoimmune/allergic encephalomyelitis (EAE) were given OPCA along with a reference drug (FTY720). Biochemical, cellular, and molecular analyses were performed in serum and brain tissues to measure anti-inflammatory and neuroprotective responses. OPCA treatment protected EAE-induced changes in mouse brains maintaining blood-brain barrier integrity and preventing inflammation. Moreover, the protein and mRNA levels of MS-related genes such as HLD-DR1, CCL5, TNF-α, IL6, and TGFB1 were significantly reduced in OPCA-treated mouse brains. Notably, the expression of genes, including PLP, MBP, and MAG, involved in the development and structure of myelin was significantly elevated in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included a substantial reduction in pro-inflammatory cytokines in the serum of treated EAE animals. Lastly, following OPCA treatment, the promoter regions for most inflammatory regulators were hypermethylated. These data support that OPCA is a valuable and appealing candidate for human MS treatment since OPCA not only normalizes the pro- and anti-inflammatory immunological bias but also stimulates remyelination in EAE. © 2023 Elsevier B.V., All rights reserved.Article Citation - WoS: 6Citation - Scopus: 6Sleep-Aware Wavelength and Bandwidth Assignment Scheme for TWDM PON(Springer, 2021-06) Butt, Rizwan Aslam; Faheem, Muhammad; Ashraf, M. Waqar; Arfeen, Asad; Memon, Kamran Ali; Khawaja, AttaullahThe energy efficiency and delay performance of PON are two inversely related phenomena. Higher sleep time of the Optical Network Units (ONUs) results in higher upstream (US) delays due to increased traffic queues during the ONU Asleep state. Although an efficient dynamic bandwidth and wavelength assignment (DWBA) scheme can decrease US delays by minimizing the bandwidth waste and improving the fairness of bandwidth distribution among the ONUs. However, the conventional DWBA schemes are not designed to work with cyclic sleep mode (CSM) and they keep on assigning bandwidth to ONUs even if the ONU is in Asleep state leading to wastage of bandwidth and degraded CSM performance. Therefore, in this work a sleep aware DWBA scheme for TWDM PON is presented to coordinate with CSM mode. It only assign bandwidth to Active ONUs during the guaranteed phase, surplus phase and excess phase allocation phases which minimizes the bandwidth waste and the bandwidth lost at the ONU end. The wavelength switching process is also improved by only considering the Active state ONUs to balance the traffic load on all the wavelengths. The simulation results support our claim as the SA-DWBA scheme on average achieves DWBA schemes due to up to 50% to 65% higher energy savings compared to other due to longer ONU Asleep times. However, the increased upstream delays of all the traffic classes in SA-DWBA scheme remain within the set delay limit of 50 ms.
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