Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Novel Statistical Approaches for Survival Analysis of RNA-Sequencing Data(Bentham Science Publ Ltd, 2026) Cephe, Ahu; Karabulut, Erdem; Zararsız, Gözde Ertürk; Sezgin, Ahmet; Koçhan, NeclaIntroduction/Objective Accurate patient survival predictions are vital for effective cancer treatments. Precision medicine uses gene expression data to improve prognosis by considering genetic variability. Predicting survival in cancer patients using high-dimensional gene expression data, such as RNA-sequencing (RNA-seq), attracted much attention in recent years. However, the literature contains limited algorithms for survival modeling that account for the high dimensionality, heterogeneity, and correlated genes of RNA-seq data. This study aims to develop novel approaches for predicting survival and identifying biomarkers using RNA-seq data.Introduction/Objective Accurate patient survival predictions are vital for effective cancer treatments. Precision medicine uses gene expression data to improve prognosis by considering genetic variability. Predicting survival in cancer patients using high-dimensional gene expression data, such as RNA-sequencing (RNA-seq), attracted much attention in recent years. However, the literature contains limited algorithms for survival modeling that account for the high dimensionality, heterogeneity, and correlated genes of RNA-seq data. This study aims to develop novel approaches for predicting survival and identifying biomarkers using RNA-seq data.Methods Survival data of RNA-seq is first transformed into binary classification data using a stacking algorithm. Then, block-based priority-Lasso and IPF-Lasso algorithms are applied to the dataset, which includes two distinct types of variables. Additionally, sample weights obtained from the voom transformation are incorporated. Our approaches, named voomStackLasso, are tested on 12 real datasets from the TCGA database. We used Harrell's concordance index and the integrated Brier score to evaluate model performance, and the number of selected features to assess model sparsity.Results The results indicated that the voomStackLasso algorithms demonstrated comparable or superior performance compared to other existing survival algorithms. Furthermore, we have introduced an R package called MLSeqSurv, which allows for the utilization of both established survival algorithms from the literature and voomStackLasso algorithms for RNA-seq data.Conclusion This study introduces two new algorithms for the survival analysis of RNA-seq data. Additionally, this study has led to new research directions for applying both existing and newly developed classification algorithms to the survival analysis of RNA-seq data.Article Identification of Potential Dual HDAC6 and HSP90 Inhibitors for the Treatment of Cancer Using Molecular Docking, Molecular Dynamics and MM/PBSA Studies: A Comprehensive In Silico Study(Bentham Science Publ Ltd, 2026) Yucel, Muhsin Samet; Akcok, IsmailBackground Histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90) are crucial therapeutic targets in cancer research with their interconnected roles in regulating protein homeostasis and cellular processes. The interaction of these proteins within the cytosolic complex plays a critical role in regulating cancer cell survival and progression. Notably, current studies highlight that the simultaneous inhibition of HDAC6 and Hsp90 can produce synergistic effects and offer a promising therapeutic potential for combating malignant cancers.Objective The objective of this study was to explore potential compounds that can inhibit both HDAC6 and Hsp90 proteins.Methods In this study, a number of in-silico computational techniques were employed. A total of 791 molecules, sharing at least 30% similarity with previously identified four HDAC inhibitors, were obtained from the ZINC15 database and subjected to docking on HDAC6 and Hsp90 proteins. The top eight ligands demonstrating the best binding scores against both targets, with panobinostat and ganetespib serving as reference compounds for HDAC6 and Hsp90, respectively, were selected for further analysis. Subsequently, ADME prediction and molecular dynamics simulations were conducted on the selected ligands.Results A detailed molecular docking, molecular dynamics simulations and ADME studies have revealed that ZINC27653366 exhibited the highest inhibitory potential against both Hsp90 and HDAC6 target proteins, making it the most promising inhibitor.Conclusion In conclusion, although additional in vitro and in vivo studies are required for the validation, in silico evaluation of ZINC27653366 may position it as a promising candidate for the treatment of different types of cancers.Article Citation - WoS: 5Citation - Scopus: 4Active Subnetwork Ga: A Two Stage Genetic Algorithm Approach to Active Subnetwork Search(Bentham Science Publ Ltd, 2017-07-11) Ozisik, Ozan; Bakir-Gungor, Burcu; Diri, Banu; Sezerman, Osman UgurBackground: A group of interconnected genes in a protein-protein interaction network that contains most of the disease associated genes is called an active subnetwork. Active subnetwork search is an NP-hard problem. In the last decade, simulated annealing, greedy search, color coding, genetic algorithm, and mathematical programming based methods are proposed for this problem. Method: In this study, we employed a novel genetic algorithm method for active subnetwork search problem. We used active node list chromosome representation, branch swapping crossover operator, multicombination of branches in crossover, mutation on duplicate individuals, pruning, and two stage genetic algorithm approach. The proposed method is tested on simulated datasets and Wellcome Trust Case Control Consortium rheumatoid arthritis genome-wide association study dataset. Our results are compared with the results of a simple genetic algorithm implementation and the results of the simulated annealing method that is proposed by Ideker et al. in their seminal paper. Results and Conclusion: The comparative study demonstrates that our genetic algorithm approach outperforms the simple genetic algorithm implementation in all datasets and simulated annealing in all but one datasets in terms of obtained scores, although our method is slower. Functional enrichment results show that the presented approach can successfully extract high scoring subnetworks in simulated datasets and identify significant rheumatoid arthritis associated subnetworks in the real dataset. This method can be easily used on the datasets of other complex diseases to detect disease-related active subnetworks. Our implementation is freely available at https://www.ce.yildiz.edu.tr/personal/ozanoz/file/6611/ActSubGA.