PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Developing a Label Propagation Approach for Cancer Subtype Classification Problem(Tubitak Scientific & Technological Research Council Turkey, 2022-01-01) Guner, Pinar; Bakir-Gungor, Burcu; Coskun, MustafaCancer is a disease in which abnormal cells grow uncontrollably and invade other tissues. Several types of cancer have various subtypes with different clinical and biological implications. Based on these differences, treatment methods need to be customized. The identification of distinct cancer subtypes is an important problem in bioinformatics, since it can guide future precision medicine applications. In order to design targeted treatments, bioinformatics methods attempt to discover common molecular pathology of different cancer subtypes. Along this line, several computational methods have been proposed to discover cancer subtypes or to stratify cancer into informative subtypes. However, existing works do not consider the sparseness of data (genes having low degrees) and result in an ill-conditioned solution. To address this shortcoming, in this paper, we propose an alternative unsupervised method to stratify cancer patients into subtypes using applied numerical algebra techniques. More specifically, we applied a label propagation based approach to stratify somatic mutation profiles of colon, head and neck, uterine, bladder, and breast tumors. We evaluated the performance of our method by comparing it to the baseline methods. Extensive experiments demonstrate that our approach highly renders tumor classification tasks by largely outperforming the state-of-the-art unsupervised and supervised approaches.Article Citation - WoS: 1Citation - Scopus: 2Tomatidine, a Steroidal Alkaloid, Synergizes With Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells(Humana Press inc, 2024-07-11) Ayvaz, Havva Berre; Yenigul, Munevver; Akcok, Emel Basak Gencer; Gencer Akçok, Emel BaşakBackgroundAcute Myeloid Leukemia (AML) is a hematological cancer that frequently presents with a range of side effects and drug resistance during anticancer drug treatment. The current study aims to achieve increased efficacy by combining lower doses of cisplatin with increasing concentrations of tomatidine in AML cells to increase efficacy.MethodsAnti-proliferative effects of single and combination of cisplatin and tomatidine were assessed via MTT cell viability assay. The Annexin V/Propidium Iodide Double Staining method was used to measure the apoptotic effects of combined tomatidine and cisplatin treatment. Then, Western Blot analysis was performed to measure Poly (ADP-ribose) polymerase (PARP) and Caspase-3 protein expression levels.ResultsCisplatin treatment with lower concentrations displayed high cytotoxic effects on AML cells, compared with tomatidine. The combination of the Inhibitory Concentration (IC) 20 value of cisplatin and increasing doses of tomatidine exhibited a significant decrease in cell viability relative to single treatments. The combination index analysis revealed a mild synergistic effect of cisplatin IC20 and varying tomatidine doses. The apoptosis induced when cisplatin was combined with 500 mu M tomatidine by almost 20%, while the percentage of apoptosis in combination with 1 mM tomatidine was measured by 50% for both cell lines. The upregulation of proapoptotic cleaved-PARP (3.2 and 1.08-fold for THP-1 and MOLM-13, respectively) and downregulation in Caspase-3 (0.23 and 0.13-fold for THP-1 and MOLM-13, respectively) was detected.ConclusionsTogether, the study indicated that when tomatidine combined with cisplatin on AML cell lines, a combinatorial anti-proliferative and apoptotic effect is observed. The combination of cisplatin with tomatidine may be a promising approach.Article Citation - WoS: 1Citation - Scopus: 1RPI-1 (Human DCDC2) Displays Functional Redundancy With Nephronophthisis 4 in Regulating Cilia Biogenesis in C. Elegans(Tubitak Scientific & Technological Research Council Turkey, 2023-01-01) Kaplan, Oktay I.Projecting from most cell surfaces, cilia serve as important hubs for sensory and signaling processes and have been linked to a variety of human disorders, including Bardet-Biedl Syndrome (BBS), Meckel-Gruber Syndrome (MKS), Nephronophthisis (NPHP), and Joubert Syndrome, and these diseases are collectively known as a ciliopathy. DCDC2 is a ciliopathy protein that localizes to cilia; nevertheless, our understanding of the role of DCDC2 in cilia is still limited. We employed C. elegans to investigate the function of C. elegans RPI-1, a Caenorhabditis elegans ortholog of human DCDC2, in cilia and found that C. elegans RPI-1 localizes to the entire ciliary axoneme, but is not present in the transition zone and basal body. We generated a null mutant of C. elegans rpi-1, and our analysis with a range of fluorescence-based ciliary markers revealed that DCDC2 and nephronophthisis 4 (NPHP-4/NPHP4) display functional redundant roles in regulating cilia length and cilia positions. Taken together, our analysis discovered a novel genetic interaction between two ciliopathy disease genes (RPI-1/DCDC2 and NPHP-4/NPHP4) in C. elegans.Article Citation - WoS: 1Citation - Scopus: 2Protocol for Determining the Average Speed and Frequency of Kinesin and Dynein-Driven Intraflagellar Transport (IFT) in C. Elegans(Elsevier, 2022-09) Turan, Merve G.; Kantarci, Hanife; Temtek, Sadiye D.; Cakici, Onur; Cevik, Sebiha; Kaplan, Oktay, IHere, we present a protocol to image a fluorescent-labeled intraflagellar trans-port (IFT) component in Caenorhabditis elegans with fluorescence microscopy, including steps of sample preparations, in vivo live-cell imaging, and post -micro-scopy analysis with kymographs. This protocol breaks down all processes into three categories: (1) pre-imaging preparations, (2) preparations for the time of image acquisition, and (3) post-imaging analyses. The protocol can be applied to determine the speed and frequency of moving particles. For complete details on the use and execution of this protocol, please refer to Cevik et al. (2021).Article Citation - WoS: 4Citation - Scopus: 4Protocol for Cell Surface Biotinylation of Magnetic Labeled and Captured Human Peripheral Blood Mononuclear Cells(Elsevier, 2022-12) Ayaz-Guner, Serife; Acar, Mustafa Burak; Boyvat, Dudu; Guner, Huseyin; Bozalan, Habibe; Guzel, Melis; Ozcan, ServetAnalysis of the surfaceome of a blood cell subset requires cell sorting, followed by surface protein enrichment. Here, we present a protocol combining magnet-ically activated cell sorting (MACS) and surface biotinylation of the target cell subset from human peripheral blood mononuclear cells (PBMCs). We describe the steps for isolating target cells and their in-column surface biotinylation, fol-lowed by isolation and mass spectrometry analysis of biotinylated proteins. The protocol enables in-column surface biotinylation of specific cell subsets with minimal membrane disruption.Article Citation - WoS: 3Citation - Scopus: 3Pericardial Fluid and Vascular Tissue Engineering: A Preliminary Study(Ios Press, 2021-03-23) Sonmezer, Dilek; Latifoglu, Fatma; Toprak, Guler; Duzler, Ayhan; Isoglu, Ismail AlperBACKGROUND: The heart is surrounded by a membrane called pericardium or pericardial cavity. OBJECTIVE: In this study, we investigated the pericardial fluid (PF) for coating polycaprolactone (PCL) scaffolds. PFS, which is a PF component, was used for the coating material. In addition to using PFS for surface coating, MED and fetal bovine serum (FBS) were also used for comparison. METHODS: Pericardial fluid cells (PFSc) isolated from PF were cultured on coated PCL scaffolds for 1, 3, and 5 days. Cell viability was determined using 3-(4, 5-di-methylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The MTT assay results showed that the viability of cells on PCL scaffold coated with PFS increased over time (P < 0.005), and cell viability was significantly different between PCL scaffolds coated with PFS and non-coated PCL scaffolds. However, cell viability was significantly higher in the PCL scaffolds coated with PFS than non-coated and coated with FBS, MED, and PCL scaffolds. Scanning electron microscopy (SEM) microscopy images and MTT assay indicated that PFSc are attached, proliferated, and spread on PCL scaffolds, especially on PCL scaffolds coated with PFS. CONCLUSIONS: These results suggest that PFS is a biocompatible material for surface modification of PCL scaffolds, which can be used as a suitable material for tissue engineering applications.Book Part Citation - Scopus: 1Measurement of Autophagic Activity in Cancer Cells With Flow Cytometric Analysis Using Cyto-Id Staining(Humana Press Inc., 2024) Şansaçar, Merve; Gencer Akçok, Emel BaşakAutophagy is an evolutionarily conserved process providing the energy that cells need to survive, especially in stress situations, through catabolic processes. Considering the dual role of autophagy in cancer cells depending on the cellular context, it is crucial to comprehend the effect of drug candidates put forward to prevent cancer through the autophagy pathway. The CYTO-ID® Autophagy Detection Kit allows a rapid, specific and quantitative measurement of autophagic activity at the cellular level using a 488 nm-excitable green fluorescent detection reagent via flow cytometer. In this chapter, we present the CYTO-ID® Autophagy Detection method with a stepwise protocol to monitor the autophagy flux after the application of any compound to suspension cancer cell lines with flow cytometric analysis. © 2025 Elsevier B.V., All rights reserved.Article Citation - WoS: 3Citation - Scopus: 3MSABrowser: Dynamic and Fast Visualization of Sequence Alignments, Variations and Annotations(Oxford Univ Press, 2021-01-01) Torun, Furkan M.; Bilgin, Halil, I; Kaplan, Oktay, ISequence alignment is an excellent way to visualize the similarities and differences between DNA, RNA or protein sequences, yet it is currently difficult to jointly view sequence alignment data with genetic variations, modifications such as post-translational modifications and annotations (i.e. protein domains). Here, we present the MSABrowser tool that makes it easy to co-visualize genetic variations, modifications and annotations on the respective positions of amino acids or nucleotides in pairwise or multiple sequence alignments. MSABrowser is developed entirely in JavaScript and works on any modern web browser at any platform, including Linux, Mac OS X and Windows systems without any installation. MSABrowser is also freely available for the benefit of the scientific community.Article Evaluation of HOTAIR, HOXD8, HOXD9, HOXD11 Gene Expression Levels in Turkish Patients With Acute and Chronic Myeloid Leukemia: A Single Center Experience(Cellular and Molecular Biology Association, 2024-11-27) Saraymen, Esma; Erdem, Yakut; Akalin, Hilal Ünlü; Taşçıoğlu, Nazife; Saraymen, Berkay; Celik, Serhat; Özkul, Yusuf T.Homeobox (HOX) transcript antisense RNA (HOTAIR) and HOX genes are reported to be more expressed in various cancers in humans in recent studies. The role of HOTAIR and HOXD genes in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is not well known. In this study, expression levels of HOXD8, HOXD9 and HOXD11 from HOXD gene family and HOTAIR were determined from peripheral blood samples of 30 AML and 30 CML patients and 20 healthy volunteers by quantitative Real Time PCR. We determined that the expression levels of HOXD9 and HOXD11 in the AML patients were significantly lower than the control group (p<0.001 and p=0.002, respectively). There was no significant difference in the expression levels of HOTAIR and HOXD8 when compared to the control group. In the CML patients there was a significant increase in the expression level of HOTAIR when compared to the control group (p=0.002). The expression levels of HOXD9 and HOXD11 were found to be significantly lower than the control group (p<0.001). Our study showed that HOTAIR may not be a biomarker in the diagnosis and is not significantly correlated with the clinicopathological prognostic characteristics of AML. Additionally; it can be said that HOTAIR is oncogenic by suppressing the expression of HOXD9 and HOXD11 but not HOXD8 in CML patients. The expression profiles of HOTAIR may be a potential biomarker in the diagnosis of CML patients in predicting and monitoring drug resistance. © 2025 Elsevier B.V., All rights reserved.Article Enlightening the Molecular Mechanisms of Type 2 Diabetes With a Novel Pathway Clustering and Pathway Subnetwork Approach(Tubitak Scientific & Technological Research Council Turkey, 2022-01-01) Bakir-Gungor, Burcu; Yazici, Miray Unlu; Goy, Gokhan; Temiz, Mustafa; Ünlü Yazici, MirayType 2 diabetes mellitus (T2D) constitutes 90% of the diabetes cases, and it is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for T2D successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multigenic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three metaanalysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in silico approaches that proceed in top-down manner and bottom-up manner, and presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, PPI networks into GWAS can dissect leading molecular pathways, and it could offer improvement over traditional enrichment strategies.