Yazar "Demirtas, Talip Yasir" seçeneğine göre listele

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    A 19-Gene Signature of Serous Ovarian Cancer Identified by Machine Learning and Systems Biology: Prospects for Diagnostics and Personalized Medicine
    (Mary Ann Liebert, Inc, 2024) Kori, Medi; Demirtas, Talip Yasir; Comertpay, Betul; Arga, Kazim Yalcin; Sinha, Raghu; Gov, Esra
    Ovarian cancer is a major cause of cancer deaths among women. Early diagnosis and precision/personalized medicine are essential to reduce mortality and morbidity of ovarian cancer, as with new molecular targets to accelerate drug discovery. We report here an integrated systems biology and machine learning (ML) approach based on the differential coexpression analysis to identify candidate systems biomarkers (i.e., gene modules) for serous ovarian cancer. Accordingly, four independent transcriptome datasets were statistically analyzed independently and common differentially expressed genes (DEGs) were identified. Using these DEGs, coexpressed gene pairs were unraveled. Subsequently, differential coexpression networks between the coexpressed gene pairs were reconstructed so as to identify the differentially coexpressed gene modules. Based on the established criteria, SOV-module was identified as being significant, consisting of 19 genes. Using independent datasets, the diagnostic capacity of the SOV-module was evaluated using principal component analysis (PCA) and ML techniques. PCA showed a sensitivity and specificity of 96.7% and 100%, respectively, and ML analysis showed an accuracy of up to 100% in distinguishing phenotypes in the present study sample. The prognostic capacity of the SOV-module was evaluated using survival and ML analyses. We found that the SOV-module's performance for prognostics was significant (p-value = 1.36 x 10-4) with an accuracy of 63% in discriminating between survival and death using ML techniques. In summary, the reported genomic systems biomarker candidate offers promise for personalized medicine in diagnosis and prognosis of serous ovarian cancer and warrants further experimental and translational clinical studies.
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    Drug repurposing for rheumatoid arthritis: Identification of new drug candidates via bioinformatics and text mining analysis
    (Taylor & Francis Ltd, 2022) Unal, Ulku; Comertpay, Betul; Demirtas, Talip Yasir; Gov, Esra
    Rheumatoid arthritis (RA) is an autoimmune disease that results in the destruction of tissue by attacks on the patient by his or her own immune system. Current treatment strategies are not sufficient to overcome RA. In the present study, various transcriptomic data from synovial fluids, synovial fluid-derived macrophages, and blood samples from patients with RA were analysed using bioinformatics approaches to identify tissue-specific repurposing drug candidates for RA. Differentially expressed genes (DEGs) were identified by integrating datasets for each tissue and comparing diseased to healthy samples. Tissue-specific protein-protein interaction (PPI) networks were generated and topologically prominent proteins were selected. Transcription-regulating biomolecules for each tissue type were determined from protein-DNA interaction data. Common DEGs and reporter biomolecules were used to identify drug candidates for repurposing using the hypergeometric test. As a result of bioinformatic analyses, 19 drugs were identified as repurposing candidates for RA, and text mining analyses supported our findings. We hypothesize that the FDA-approved drugs momelotinib, ibrutinib, and sodium butyrate may be promising candidates for RA. In addition, CHEMBL306380, Compound 19a (CHEMBL3116050), ME-344, XL-019, TG100801, JNJ-26483327, and NV-128 were identified as novel repurposing candidates for the treatment of RA. Preclinical and further validation of these drugs may provide new treatment options for RA.
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    Forecasting Gastric Cancer Diagnosis, Prognosis, and Drug Repurposing with Novel Gene Expression Signatures
    (Mary Ann Liebert, Inc, 2022) Demirtas, Talip Yasir; Rahman, Md Rezanur; Yurtsever, Merve Capkin; Gov, Esra
    Gastric cancer (GC) is a prevalent disease worldwide with high mortality and poor treatment success. Early diagnosis of GC and forecasting of its prognosis with the use of biomarkers are directly relevant to achieve both personalized/precision medicine and innovation in cancer therapeutics. Gene expression signatures offer one of the promising avenues of research in this regard, as well as guiding drug repurposing analyses in cancers. Using publicly accessible gene expression datasets from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), we report here original findings on co-expressed gene modules that are differentially expressed between 133 GC samples and 46 normal tissues, and thus hold potential for novel diagnostic candidates for GC. Furthermore, we found two co-expressed gene modules were significantly associated with poor survival outcomes revealed by survival analysis of the RNA-Seq TCGA datasets. We identified STAT6 (signal transducer and activator of transcription 6) as a key regulator of the identified gene modules. Finally, potential therapeutic drugs that may target and reverse the expression of the identified altered gene modules examined for drug repurposing analyses and the unraveled compounds were further investigated in the literature by the text mining method. Accordingly, we found several repurposed drug candidates, including Trichostatin A, Vorinostat, Parthenolide, Panobinostat, Brefeldin A, Belinostat, and Danusertib. Through text mining analysis and literature search validation, Belinostat and Danusertib were suggested as possible novel drug candidates for GC treatment. These findings collectively inform multiple aspects of GC medical management, including its precision diagnosis, forecasting of possible outcomes, and drug repurposing for innovation in GC medicines in the future.