Yıl: 2022 Cilt: 46 Sayı: 4 Sayfa Aralığı: 318 - 341 Metin Dili: İngilizce DOI: 10.55730/1300-0152.2620 İndeks Tarihi: 05-12-2022

Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach

Öz:
Type 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.
Anahtar Kelime: Genome-wide association study (GWAS) multiple association studies single nucleotide polymorphism (SNP) subnetwork identification pathway subnetwork pathway clustering analysis type 2 diabetes

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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APA Bakir-Gungor B, YAZICI M, Goy G, Temiz M (2022). Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. , 318 - 341. 10.55730/1300-0152.2620
Chicago Bakir-Gungor Burcu,YAZICI Miray ÜNLÜ,Goy Gokhan,Temiz Mustafa Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. (2022): 318 - 341. 10.55730/1300-0152.2620
MLA Bakir-Gungor Burcu,YAZICI Miray ÜNLÜ,Goy Gokhan,Temiz Mustafa Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. , 2022, ss.318 - 341. 10.55730/1300-0152.2620
AMA Bakir-Gungor B,YAZICI M,Goy G,Temiz M Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. . 2022; 318 - 341. 10.55730/1300-0152.2620
Vancouver Bakir-Gungor B,YAZICI M,Goy G,Temiz M Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. . 2022; 318 - 341. 10.55730/1300-0152.2620
IEEE Bakir-Gungor B,YAZICI M,Goy G,Temiz M "Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach." , ss.318 - 341, 2022. 10.55730/1300-0152.2620
ISNAD Bakir-Gungor, Burcu vd. "Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach". (2022), 318-341. https://doi.org/10.55730/1300-0152.2620
APA Bakir-Gungor B, YAZICI M, Goy G, Temiz M (2022). Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. Turkish Journal of Biology, 46(4), 318 - 341. 10.55730/1300-0152.2620
Chicago Bakir-Gungor Burcu,YAZICI Miray ÜNLÜ,Goy Gokhan,Temiz Mustafa Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. Turkish Journal of Biology 46, no.4 (2022): 318 - 341. 10.55730/1300-0152.2620
MLA Bakir-Gungor Burcu,YAZICI Miray ÜNLÜ,Goy Gokhan,Temiz Mustafa Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. Turkish Journal of Biology, vol.46, no.4, 2022, ss.318 - 341. 10.55730/1300-0152.2620
AMA Bakir-Gungor B,YAZICI M,Goy G,Temiz M Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. Turkish Journal of Biology. 2022; 46(4): 318 - 341. 10.55730/1300-0152.2620
Vancouver Bakir-Gungor B,YAZICI M,Goy G,Temiz M Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach. Turkish Journal of Biology. 2022; 46(4): 318 - 341. 10.55730/1300-0152.2620
IEEE Bakir-Gungor B,YAZICI M,Goy G,Temiz M "Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach." Turkish Journal of Biology, 46, ss.318 - 341, 2022. 10.55730/1300-0152.2620
ISNAD Bakir-Gungor, Burcu vd. "Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach". Turkish Journal of Biology 46/4 (2022), 318-341. https://doi.org/10.55730/1300-0152.2620