Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - WoS: 1Citation - Scopus: 1Enlightening 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.Conference Object Nöromüsküler Hastalıkların Ortak MikroRNA ve Yolaklarının İn Siliko Yöntemlerle Belirlenmesi(Institute of Electrical and Electronics Engineers Inc., 2019-04) Ünlü Yazici, Miray; Aksu-Menges, Evrim; Akkaya-Ulum, Yeliz Z.; Balcihayta, Burcu; Bakir-Güngör, BurcuNeuromuscular disorders (NMD) are a heterogeneous group of diseases characterized by the loss of function of the peripheral nerves and muscles. However, there are no effective and widespread therapeutic approaches to prevent or delay the progression of these disease types. MicroRNAs (miRNAs) which cause significant changes in gene expression by binding to target messenger RNAs (mRNAs), are known to have an effect on disease mechanisms. In this study, by integrating different bioinformatics methods, we aim to find miRNAs, target genes and pathways related to a group of neuromuscular diseases. For this purpose, we determined 17 miRNAs that show significant expression changes between patient and healthy groups; predicted target genes of these miRNAs; and identified affected pathways using subnetwork discovery, functional enrichment based algorithms. In our study, we integrated different in-silico approaches that proceed in topdown manner or bottom-up manner. The identified candidate miRNAs, genes and pathways, which could help to explain neuromuscular disease development mechanisms, are now under investigation in wet-lab. © 2020 Elsevier B.V., All rights reserved.Conference Object Citation - WoS: 1Citation - Scopus: 1Kolon Kanserinde Etkilenen Yolak Alt Ağlarini Ve Kümelenmelerini Belirlemek için Yeni Bir Yöntem(Institute of Electrical and Electronics Engineers Inc., 2019-09) Göy, Gökhan; Ünlü Yazici, Miray; Bakir-Güngör, BurcuNowadays new technological developments that play an important role in the production of big data have brought about the interpretation, sharing and storage of data related to complex diseases. Combining multi-omic data in different molecular levels is potentially important for understanding the biological origin of complex diseases. One of these complex diseases is cancer of different types, which has one of the highest causes of death worldwide. The integration of multiple omic data in the framework of a comprehensive analysis and identification of relevant pathways contribute to the development of therapeutic approaches related to disease. In this study, RNA and methylation data (genes and p values) of colon adenocarcinoma were obtained from TCGA data portal and combined with Fisher's method. While protein subnetworks affected by the disease were identified by using subnetwork algorithm, pathways related to the disease and genes associated with these pathways were determined by functional enrichment analysis. Using gene-pathway relationship matrix, kappa scores of pathways were determined by similarity calculation. In this way, the pathways were clustered according to the hierarchically optimal number, as a result, the most important pathway clusters and related genes that are effective in disease formation identified. © 2020 Elsevier B.V., All rights reserved.