TR-Dizin İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396
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Article Developing a Label Propagation Approach for Cancer Subtype Classification Problem(TUBITAK, 2021) Güner, P.; Bakir-Güngör, B.; Coşkun, M.; Şahan, Pınar GünerCancer 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. © 2022 Elsevier B.V., All rights reserved.Article Citation - WoS: 8Citation - Scopus: 10Lung Cancer Subtype Differentiation From Positron Emission Tomography Images(Tubitak Scientific & Technological Research Council Turkey, 2020-01-27) Ayyildiz, Oguzhan; Aydin, Zafer; Yilmaz, Bulent; Karacavus, Seyhan; Senkaya, Kubra; Icer, Semra; Kaya, Eser; Taşdemir, ArzuLung cancer is one of the deadly cancer types, and almost 85% of lung cancers are nonsmall cell lung cancer (NSCLC). In the present study we investigated classification and feature selection methods for the differentiation of two subtypes of NSCLC, namely adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The major advances in understanding the effects of therapy agents suggest that future targeted therapies will be increasingly subtype specific. We obtained positron emission tomography (PET) images of 93 patients with NSCLC, 39 of which had ADC while the rest had SqCC. Random walk segmentation was applied to delineate three-dimensional tumor volume, and 39 texture features were extracted to grade the tumor subtypes. We examined 11 classifiers with two different feature selection methods and the effect of normalization on accuracy. The classifiers we used were the k-nearest-neighbor, logistic regression, support vector machine, Bayesian network, decision tree, radial basis function network, random forest, AdaBoostM1, and three stacking methods. To evaluate the prediction accuracy we performed a leave-one-out cross-validation experiment on the dataset. We also considered optimizing certain hyperparameters of these models by performing 10-fold cross-validation separately on each training set. We found that the stacking ensemble classifier, which combines a decision tree, AdaBoostM1, and logistic regression methods by a metalearner, was the most accurate method for detecting subtypes of NSCLC, and normalization of feature sets improved the accuracy of the classification method.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.