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: 6Citation - Scopus: 6Sex Effect on the Correlation of Immunoglobulin G Glycosylation With Rheumatoid Arthritis Disease Activity(Tubitak Scientific & Technological Research Council Turkey, 2020-12-14) Ercan, AltanRheumatoid arthritis (RA) is a chronic autoimmune disease which affects females more than males with a presence of autoantibodies. Immunoglobulin G (IgG) produced by adaptive arm has 2 functional domains, Fc and Fab. The Fc domain binds Fc gamma receptors and C1q proteins of the innate arm. Therefore, the IgG Fc domain serves as a bridge between the innate and adaptive arms and is regulated by an evolutionarily conserved N-glycosylation with variable structures. These glycans are classified as agalactosylated G0, monogalactosylated G1, and digalactosylated G2, which are further modified by core-fucosylation (F) and bisecting N-acetylglucosamine (B) moieties such as G0F and G0FB. Interestingly, proinflammatory G0F is shown to be regulated by estrogen in vivo. Here, it is hypothesized that the regulation of G0F by estrogen contributes to sex dichotomy in RA by setting up the level of IgG-dependent inflammation and therefore, RA disease activity (Das28-CRP3). To investigate this hypothesis, IgG glycosylation was characterized in serum samples from active RA patients (n = 232) and healthy controls (n = 232) by serum N-glycan analysis using the high performance liquid chromatography. According to the results, the IgG Fc glycan phenotype originates predominantly from the structure of G0F, and both G0F and G0FB correlate with Das28-CRP3 in females, but not in males. In conclusion, IgG G0F-dependent inflammation differs in males and females, and these differences point to the differential regulation of inflammation by sex hormone estrogen via IgG glycosylation.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.Editorial Citation - WoS: 3Citation - Scopus: 4Precision Medicine in Oncology: Challenges, Stakes and New Paradigms(John Libbey Eurotext Ltd, 2019-02) Cox, Stephanie; Rousseau-Tsangaris, Marina; Abou-Zeid, Nancy; Dalle, Stephane; Leurent, Pierre; Cutivet, Arnaud; Denefle, PatriceArticle Citation - WoS: 4Citation - Scopus: 6One-Pot Conjugated Linoleic Acid Production From Castor Oil by Rhizopus Oryzae Lipase and Resting Cells of Lactobacillus Plantarum(Taylor & Francis Ltd, 2017-10-03) Khaskheli, Abid Ali; Talpur, Farah Naz; Aydin, Aysun Cebeci; Jawaid, Sana; Surhio, Muhammad Ali; Afridi, Hassan ImranConjugated linoleic acid (CLA) has attracted as novel type of fatty acids having unusual health-promoting properties such as anticarcinogenic and antiobesitic effects. The present work employed castor oil as substrate for one-pot production of CLA using washed cells of Lactobacillus plantarum (L. plantarum) and lipases as catalysts. Among the screened lipases, the lipase Rhizopus oryzae (ROL) greatly assisted resting cells to produce CLA. Mass spectral analysis of the product showed that two major isomers of CLA were produced in the reaction mixture i.e. cis-9, trans-11 56.55% and trans-10, cis-12 43.45%. Optimum factors for CLA synthesis were found as substrate concentration (8mg/mL), pH (6.5), washed cell concentration (12% w/v), and incubation time of 20h. Hence, the combination of ROL with L. plantarum offers one pot production of CLA selectively using castor oil as a cost-effective substrate.Article Citation - WoS: 3Citation - Scopus: 3MicroRNA Prediction Based on 3D Graphical Representation of RNA Secondary Structures(Tubitak Scientific & Technological Research Council Turkey, 2019-08-05) Sacar Demirci, Muserref Duygu; Demirci, Müşerref Duygu SaçarMicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. While a miRNA can target hundreds of messenger RNA (mRNAs), an mRNA can be targeted by different miRNAs, not to mention that a single miRNA might have various binding sites in an mRNA sequence. Therefore, it is quite involved to investigate miRNAs experimentally. Thus, machine learning (ML) is frequently used to overcome such challenges. The key parts of a ML analysis largely depend on the quality of input data and the capacity of the features describing the data. Previously, more than 1000 features were suggested for miRNAs. Here, it is shown that using 36 features representing the RNA secondary structure and its dynamic 3D graphical representation provides up to 98% accuracy values. In this study, a new approach for ML-based miRNA prediction is proposed. Thousands of models are generated through classification of known human miRNAs and pseudohairpins with 3 classifiers: decision tree, naive Bayes, and random forest. Although the method is based on human data, the best model was able to correctly assign 96% of nonhuman hairpins from MirGeneDB, suggesting that this approach might be useful for the analysis of miRNAs from other species.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 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.