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TURANLI, BESTE

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TURANLI

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BESTE

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2013 - 2019112020 - 202319
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    Transcriptomic-Guided Drug Repositioning Supported by a New Bioinformatics Search Tool: geneXpharma
    (MARY ANN LIEBERT, INC, 2017) TURANLI, BESTE; Turanli, Beste; Gulfidan, Gizem; Arga, Kazim Yalcin
    Drug repositioning is an innovative approach to identify new therapeutic indications for existing drugs. Drug repositioning offers the promise of reducing drug development timeframes and costs, and because it involves drugs that are already in the clinic, it might remedy some of the drug safety challenges traditionally associated with drug candidates that are not yet available in the clinic. The gene-by-drug interactions are an important dimension of optimal drug repositioning and development strategies. While gene-by-drug interactions have been curated and presented in various databases, novel bioinformatics tools and approaches are timely, and required with a specific focus to support drug positioning. We report, in this study, the design of a public web-accessible transcriptomic-/gene expression-guided pharmaceuticals search tool, geneXpharma (www.genexpharma.org). GeneXpharma is a public platform with user-centric interface that provides statistically evaluated gene expressions and their drug interactions for 48 diseases under seven different disease categories. GeneXpharma is designed and organized to generate hypotheses on druggable genome within the disease-gene-drug triad and thus, help repositioning of drugs against diseases. The search system accommodates various entry points using drugs, genes, or diseases, which then enable researchers to extract drug repurposing candidates and readily export for further evaluation. Future developments aim to improve the geneXpharma algorithm, enrich its content, and enhance the website interface through addition of network visualizations and graphical display items. Bioinformatics search tools can help enable the convergence of drug repositioning and gene-by-drug interactions so as to further optimize drug development efforts in the future.
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    Drug repositioning for cancer therapy by the employment of systems biology
    (2019-10-01) TURANLI, BESTE; ARĞA, KAZIM YALÇIN; TURANLI B., GULFİDAN G., Mardinoğlu A., ARĞA K. Y.
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    Comparative study on understanding molecular signatures of ALL and philedelphia positive ALL in adults
    (2022-11-16) TURANLI, BESTE; BUDAK B., KİRAZ Y., TURANLI B.
    Acute lymphoblastic leukemia (ALL) is known to be a very heterogeneous disease together with identified various genetic abnormalities that causes the disease to be formed. ALL is also known with its low survival rates. The most commonly seen subtype of ALL is Philadelphia positive ALL (Ph+ALL) which carries BCR/ABL translocation which is considered as high-risk and the most aggressive subtype. Ph+ ALL subtype presents drug resistance phenomenon as an obstacle in the treatment process. Moreover, there has not been novel treatments developed or proposed for the treatment of ALL. In this study, we aimed to compare the molecular profiles of ALL and Ph+ALL by integrating data from multiple biomolecular levels. We statistically analyzed 8 ALL and 4 Ph+ALL-associated transcriptomic datasets using the R/Bioconductor (www.bioconductor.org) software platform. As a result of this meta-analysis, we found 799 differentially expressed genes (DEGs) for ALL and 295 DEGs for Ph+ALL. We associated DEGs with reporter molecules receptor, transcription factor, miRNA, metabolites in addition to reconstruction of protein-protein interaction networks. We also identified hub proteins according to degree and betweenness centrality. CDKN1A, HSP90AA1, PCNA, PIK3R1, SMARCA4, YWHAB, and YWHAE in ALL; LYN and RANBP9 in Ph+ALL were prominent as hub proteins. In addition, we aimed to find a novel and effective therapeutics by using drug repurposing strategy. The results elucidated by this project will further use in in vitro validation tests and may pave the way for new clinical trials and clinical applications.
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    Differential Protein Interactome in Esophageal Squamous Cell Carcinoma Offers Novel Systems Biomarker Candidates with High Diagnostic and Prognostic Performance
    (MARY ANN LIEBERT, INC, 2021) TURANLI, BESTE; Gulfidan, Gizem; Beklen, Hande; Sinha, Indu; Kucukalp, Fulya; Caloglu, Buse; Esen, Ipek; Turanli, Beste; Ayyildiz, Dilara; Arga, Kazim Yalcin; Sinha, Raghu
    Esophageal squamous cell carcinoma (ESCC) is among the most dangerous cancers with high mortality and lack of robust diagnostics and personalized/precision therapeutics. To achieve a systems-level understanding of tumorigenesis, unraveling of variations in the protein interactome and determination of key proteins exhibiting significant alterations in their interaction patterns during tumorigenesis are crucial. To this end, we have described differential protein-protein interactions and differentially interacting proteins (DIPs) in ESCC by utilizing the human protein interactome and transcriptome. Furthermore, DIP-centered modules were analyzed according to their potential in elucidation of disease mechanisms and improvement of efficient diagnostic, prognostic, and treatment strategies. Seven modules were presented as potential diagnostic, and 16 modules were presented as potential prognostic biomarker candidates. Importantly, our findings also suggest that 30 out of the 53 repurposed drugs were noncancer drugs, which could be used in the treatment of ESCC. Interestingly, 25 of these, proposed as novel drug candidates here, have not been previously associated in a context of esophageal cancer. In this context, risperidone and clozapine were validated for their growth inhibitory potential in three ESCC lines. Our findings offer a high potential for the development of innovative diagnostic, prognostic, and therapeutic strategies for further experimental studies in line with predictive diagnostics, targeted prevention, and personalization of medical services in ESCC specifically, and personalized cancer care broadly.
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    A novel levansucrase purified from halophilic bacteria halomonas smyrnensis AAD6T
    (2013-04-24) TURANLI, BESTE; ARĞA, KAZIM YALÇIN; TOKSOY ÖNER, EBRU; TURANLI B., ARĞA K. Y., TOKSOY ÖNER E.
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    Network-based approach to identify molecular signatures and therapeutic agents in Alzheimer's disease
    (ELSEVIER SCI LTD, 2019) TURANLI, BESTE; Rahman, Md. Rezanur; Islam, Tania; Turanli, Beste; Zaman, Toyfiquz; Faruquee, Hossain Md.; Rahman, Md. Mafizur; Mollah, Md. Nurul Haque; Nanda, Ranjan Kumar; Arga, Kazim Yalcin; Gov, Esra; Moni, Mohammad Ali
    Alzheimer's disease (AD) is a dynamic degeneration of the brain with progressive dementia. Considering the uncertainties in its molecular mechanism, in the present study, we employed network-based integrative analyses, and aimed to explore the key molecules and their associations with small drugs to identify potential biomarkers and therapeutic agents for the AD. First of all, we studied a transcriptome dataset and identified 1521 differentially expressed genes (DEGs). Integration of transcriptome data with protein-protein and transcriptional regulatory interactions resulted with central (hub) proteins (UBA52, RAC1, CREBBP, AR, RPS11, SMAD3, RPS6, RPL12, RPL15, and UBC), regulatory transcription factors (FOXCl, GATA2, YY1, FOXL1, NFIC, E2F1, USF2, SRF, PPARG, and JUN) and microRNAs (mir-335-5p, mir-26b-5p, mir-93-5p, mir-124-3p, mir-17-5p, mir-16-5p, mir-20a-5p, mir-92a-3p, mir-106b-5p, and mir-192-5p) as key signaling and regulatory molecules associated with transcriptional changes for the AD. Considering these key molecules as potential therapeutic targets and Connectivity Map (CMap) architecture, candidate small molecular agents (such as STOCK1N-35696) were identified as novel potential therapeutics for the AD. This study presents molecular signatures at RNA and protein levels which might be useful in increasing discernment of the molecular mechanisms, and potential drug targets and therapeutics to design effective treatment strategies for the AD.
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    Past, present, and future of therapies for pituitary neuroendocrine tumors: need for omics and drug repositioning guidance
    (2022-03-01) ERDOĞAN, ONUR; ARĞA, KAZIM YALÇIN; BOZKURT, SÜHEYLA; BAYRAKLI, FATİH; YILMAZ, BETÜL; TURANLI, BESTE; Aydin B., Yildirim E., ERDOĞAN O., ARĞA K. Y., Yilmaz B., BOZKURT S., BAYRAKLI F., TURANLI B.
    Innovation roadmaps are important, because they encourage the actors in an innovation ecosystem to creatively imagine multiple possible science future(s), while anticipating the prospects and challenges on the innovation trajectory. In this overarching context, this expert review highlights the present unmet need for therapeutic innovations for pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas. Although there are many drugs used in practice to treat PitNETs, many of these drugs can have negative side effects and show highly variable outcomes in terms of overall recovery. Building innovation roadmaps for PitNETs\" treatments can allow incorporation of systems biology approaches to bring about insights at multiple levels of cell biology, from genes to proteins to metabolites. Using the systems biology techniques, it will then be possible to offer potential therapeutic strategies for the convergence of preventive approaches and patient-centered disease treatment. Here, we first provide a comprehensive overview of the molecular subtypes of PitNETs and therapeutics for these tumors from the past to the present. We then discuss examples of clinical trials and drug repositioning studies and how multi-omics studies can help in discovery and rational development of new therapeutics for PitNETs. Finally, this expert review offers new public health and personalized medicine approaches on cases that are refractory to conventional treatment or recur despite currently used surgical and/or drug therapy.
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    Systems biology perspective of gender biases in papillary thyroid cancer diagnosis, prognosis and therapy
    (2023-10-11) TURANLI, BESTE; TURANLI B.
    Papillary thyroid cancer (PTC) represents the most prevalent form of thyroid malignancy, and its early detection holds paramount importance for effective treatment. Numerous factors, including age, gender, and exposure to radiation, can contribute to an increased risk of thyroid cancer. Although thyroid cancer can manifest at any age, women in their 40s or 50s face a higher risk compared to men, who typically present with the disease in their 60s or 70s. Additionally, thyroid cancer occurs approximately three times more frequently in women than in men. This study endeavors to elucidate the potential biomolecular signatures responsible for the gender disparity observed in PTC patients. To achieve this, four microarray datasets containing normal thyroid and PTC samples were utilized to identify gene expression signatures. Through a meta-analysis, common differentially expressed genes were discerned independently for both genders. Reporter molecules were then determined by mapping mRNA expression data across various biological levels, including transcriptional regulatory networks, protein-protein interactions, and metabolic pathways. Functional enrichment analysis was subsequently employed to identify relevant biological processes, molecular functions, signaling pathways, and metabolic routes. The study further explored the prognostic potential of the identified reporter molecules through survival analyses. Consequently, this investigation reports candidate biomolecules in each gender cohort that may serve as valuable prognostic biomarkers or potential therapeutic targets for personalized medical interventions in PTC patients.
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    Transcriptomics-based drug repurposing unravels novel therapeutic strategies in AML
    (2022-11-16) TURANLI, BESTE; ARĞA, KAZIM YALÇIN; YILMAZ, BETÜL; KELEŞOĞLU N., Korkmaz N. S., TURANLI B., ARĞA K. Y., YILMAZ B., ATEŞ DURU Ö.
    Acute myeloid leukemia (AML) is a disease of the hematopoietic system in which abnormal cells multiply rapidly, accumulate in the blood and bone marrow, and prevent the production of healthy blood cells. To date, first-line treatment of AML has been based primarily on conventional chemotherapy. Despite progress, the rate of complete remission in AML remains low, especially in older patients, and the relapse rate after complete remission remains high. The combination of clinical and laboratory data has been shown to play an important role in the development of new therapeutic strategies in AML, in addition to features of tumor histopathogenesis and transcriptional regulation. 1 Therefore, we integrated transcriptomics data from relapsed, refractory, and previously untreated AML patients based on their response to therapy using disease-specific signatures with biological and pharmacological data to enable rational identification of the potential of signaling pathways and drugs in AML. Based on the integration of transcriptomics data, we identified eight drug candidates by repurposing and evaluated their potential by in vitro testing in the HL60 and KG -1 cell lines. Six repurposed drugs, including nortriptyline, desipramine, doxepin, estramustine, risedronate, and hydrochlorothiazide, were proposed as potential drug candidates for the treatment of AML. We confirmed possible mechanisms of action of the drugs on cell viability HL -60 and KG -1 by apoptosis assays and Western blotting. Given the beneficial effects of the drugs on the apoptosis pathway, our results are intriguing and suggest that these therapies may prove useful and be potential candidates for the future treatment of AML.