Browsing by Author "Yazici, Miray Unlu"

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Enlightening the Molecular Mechanisms of Type 2 Diabetes With a Novel Pathway Clustering and Pathway Subnetwork Approach
(Tubitak Scientific & Technological Research Council Turkey, 2022) Bakir-Gungor, Burcu; Yazici, Miray Unlu; Goy, Gokhan; Temiz, Mustafa; 01. Abdullah Gül University; 02. 04. Bilgisayar Mühendisliği; 02. Mühendislik Fakültesi; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
In-Silico Methods to Identify Common MicroRNAs and Pathways of Neuromuscular Diseases
(IEEE, 345 E 47TH ST, NEW YORK, NY 10017 USA, 2019) Yazici, Miray Unlu; Menges, Evrim Aksu; Ulum, Yeliz Z. Akkaya; Hayta, Burcu Balci; Bakir-Gungor, Burcu; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; 01. Abdullah Gül University; 02. 04. Bilgisayar Mühendisliği; 02. Mühendislik Fakültesi; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Neuromuscular 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 top-down 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.
Citation - WoS: 13
Citation - Scopus: 18
Invention of 3Mint for Feature Grouping and Scoring in Multi-Omics
(Frontiers Media S.A., 2023) Yazici, Miray Unlu; Marron, J. S.; Bakir-Gungor, Burcu; Zou, Fei; Yousef, Malik; 01. Abdullah Gül University; 02. 04. Bilgisayar Mühendisliği; 02. Mühendislik Fakültesi; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Advanced genomic and molecular profiling technologies accelerated the enlightenment of the regulatory mechanisms behind cancer development and progression, and the targeted therapies in patients. Along this line, intense studies with immense amounts of biological information have boosted the discovery of molecular biomarkers. Cancer is one of the leading causes of death around the world in recent years. Elucidation of genomic and epigenetic factors in Breast Cancer (BRCA) can provide a roadmap to uncover the disease mechanisms. Accordingly, unraveling the possible systematic connections between-omics data types and their contribution to BRCA tumor progression is crucial. In this study, we have developed a novel machine learning (ML) based integrative approach for multi-omics data analysis. This integrative approach combines information from gene expression (mRNA), MicroRNA (miRNA) and methylation data. Due to the complexity of cancer, this integrated data is expected to improve the prediction, diagnosis and treatment of disease through patterns only available from the 3-way interactions between these 3-omics datasets. In addition, the proposed method bridges the interpretation gap between the disease mechanisms that drive onset and progression. Our fundamental contribution is the 3 Multi-omics integrative tool (3Mint). This tool aims to perform grouping and scoring of groups using biological knowledge. Another major goal is improved gene selection via detection of novel groups of cross-omics biomarkers. Performance of 3Mint is assessed using different metrics. Our computational performance evaluations showed that the 3Mint classifies the BRCA molecular subtypes with lower number of genes when compared to the miRcorrNet tool which uses miRNA and mRNA gene expression profiles in terms of similar performance metrics (95% Accuracy). The incorporation of methylation data in 3Mint yields a much more focused analysis. The 3Mint tool and all other supplementary files are available at .
A New Method to Identify Affected Pathway Subnetworks and Clusters in Colon Cancer
(IEEE, 345 E 47TH ST, NEW YORK, NY 10017 USA, 11092019) Goy, Gokhan; Yazici, Miray Unlu; Bakir-Gungor, Buren; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Nowadays 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.