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 Colorectal Cancer Prediction via Applying Recursive Cluster Elimination With Intra-Cluster Feature Elimination on Metagenomic Pathway Data(Springer International Publishing AG, 2024) Temiz, Mustafa; Kuzudisli, Cihan; Yousef, Malik; Bakir-Gungor, BurcuAdvances in next-generation sequencing and in "-omics" technologies enable the characterization of the human gut microbiome. Colorectal cancer (CRC), the third most common cancer worldwide, is caused by genetic mutations, environmental influences, and abnormalities in the gut microbiota. The aim of this study is to identify pathways that influence host metabolism in CRC patients. The CRC-related metagenomic dataset used in this study contains the relative abundance values of 551 pathways calculated for 1262 samples. Here, two different approaches based on the feature grouping reduce the number of features by considering relevant features as groups, eliminate irrelevant features, and perform classification. The recursive cluster elimination with intra-cluster feature elimination (RCE-IFE) approach achieves anAUCof 0.72 using an average of 66.2 features on CRC-associated metagenomics dataset. In these experiments, P163-PWY: L-lysine fermentation to acetate and butanoate and PWY-6151: S-adenosyl-L-methionine cycle I pathways are identified as potential biomarkers associated with CRC. These experiments also reduce the number of features reported by both approaches in P163-PWY: L-lysine fermentation to acetate and butanoate and PWY-6151: Sadenosyl-L-methionine cycle I pathways reported by both approaches are considered possible CRC-related biomarkers. This study contributes to the molecular diagnosis and treatment of colorectal cancer by revealing the pathways associated with CRC. Our results are promising for the study of the gut microbiota and its role in CRC.