Biyoenformatik ve Genetik Bölümü Makale Koleksiyonu
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Öğe Diagnosis of primary immunodeficiency diseases in pediatric patients hospitalized for recurrent, severe, or unusual infections(Codon Publications, 2022) Nepesov, Serdar; Fırtına, Sinem; Aygün, Fatma Deniz; Burtenece, Nihan; Çokuğraş, Haluk; Camcıoğlu, YıldızBackground: Primary immunodeficiency diseases (PID) usually presents itself with recurrent, severe, and unusual infections, along with autoimmunity and various other malignancies. But, the diversity of PID often makes the diagnosis of patients difficult for physicians other than clinical immunologists. This study aimed to describe the characteristics of patients diagnosed with PIDs during the inpatient treatment for infectious diseases, and to highlight the cases in which a PID diagnosis should be considered.Methods: The clinical, immunological, and molecular features of 81 pediatric patients treated for infectious diseases, who were diagnosed with a PID during hospitalization was retrospec-tively analyzed. The diagnosis was based on the PID criteria of the International Union of Immunological Societies.Results: The five main PID sub-types were identified. Predominantly, antibody deficiencies were the most common (61.7%) group. The average delay in diagnosis was 34.6 months, and the positive family history rate was 24.7%, while the consanguineous marriage rate was 45.7%. Around thirty-five (43%) patients were found to have mutated PID-related genes. While lower respiratory tract infections were the most common symptom, a fever of unknown origin was another remarkable diagnosis. Eight (9.9%) patients underwent allogeneic hematopoietic stem cell transplantation.Conclusions: Clinicians should consider a PID diagnosis, especially in the cases of recurrent, severe, or atypical infections. Increased knowledge of the alarm features of PID can promote early diagnosisÖğe Performing the comparative analysis to understand the functional roles of genes in different pathways of cardiomyopathy disease(Elsevier, 2021) Atak, Evren; Karaoğlu, Dilara; Serttürk, Seda; Koyuncu Irmak, Duygu; Yenenler-Kutlu, AslıPersonalized medicine is one of the popular approaches in biological sciences. Due to the great attention in personalized medicine, there exists a need for health decision algorithms developed through high-level pro-gramming languages that already compromised the statistical analyses and numerical computations. Here, we present a tool that enables us to facilitate making research in the PubMed database by classifying the scientific literature from the published abstracts and then performed the comparative analysis to highlight the importance of gene-variant relationships in the decision steps. After retrieving related genes from literature, we performed pathway analysis with them by using computer-based tools to differentiate these sub-pathways in cardiomy-opathy disease that are listed as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathy. Then, the pathogenic variants existing in these genes at each sub-pathway are retrieved, and the mechanistic interpretation about them has been gained to explain more about the differences in genes’ mode of action. Lastly, the need of structure-based studies to explain the etiology of the disease has been emphasized by providing the protein structures of related genes as a guide. This study presents the importance of combining the text-mining approach with the bioinformatics tool in effective manner both for catching up with the updated literature and for revealing newly identified genes or pathways.Öğe Identifying and elucidating the roles of Y198N and Y204F mutations in the PAH enzyme through molecular dynamic simulations(Taylor And Francis, 2021) Aslan, Tolga; Yenenler-Kutlu, Aslı; Gerlevik, Umut; Aktuğlu Zeybek, Ayşe Çiğdem; Kıykım, Ertuğrul; Sezerman, Osman UğurABSTRACT Phenylketonuria is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase gene. In phenylketonuria causes various symptoms including severe mental retardation. PAH gene of a classical Phenylketonuria patient was sequenced, and two novel heterozygous mutations, p.Y198N and p.Y204F, were found. This study aimed to reveal the impacts of these variants on the structural stability of the PAH enzyme. In-silico analyses using prediction tools and molecular dynamics simulations were performed. Mutations were introduced to the wild type catalytic monomer and full length tetramer crystal structures. Variant pathogenicity analyses predicted p.Y198N to be damaging, and p.Y204F to be benign by some prediction tools and damaging by others. Simulations suggested p.Y198N mutation cause significant fluctuations in the spatial organization of two catalytic residues in the temperature accelerated MD simulations with the monomer and increased root-mean-square deviations in the tetramer structure. p.Y204F causes noticeable changes in the spatial positioning of T278 suggesting a possible segregation from the catalytic site in temperature accelerated MD simulations with the monomer. This mutation also leads to increased root-mean-square fluctuations in the regulatory domain which may lead to conformational change resulting in inhibition of dimerization and enzyme activation. Our study reports two novel mutations in the PAH gene and gives insight to their effects on the PAH activity. MD simulations did not yield conclusive results that explains the phenotype but gave plausible insight to possible effects which should be investigated further with in-silico and in-vitro studies to assess the roles of these mutations in etiology of PKU.
