IntroductionIn gynecologic oncology, ovarian cancer is a great clinical challenge. Because of the lack of typical symptoms and effective biomarkers for noninvasive screening, most patients develop advanced-stage ovarian cancer by the time of diagnosis. MicroRNAs (miRNAs) are a type of non-coding RNA molecule that has been linked to human cancers. Specifying diagnostic biomarkers to determine non-cancer and cancer samples is difficult.MethodsBy using Boruta, a novel random forest-based feature selection in the machine-learning techniques, we aimed to identify biomarkers associated with ovarian cancer using cancerous and non-cancer samples from the Gene Expression Omnibus (GEO) database: GSE106817. In this study, we used two independent GEO data sets as external validation, including GSE113486 and GSE113740. We utilized five state-of-the-art machine-learning algorithms for classification: logistic regression, random forest, decision trees, artificial neural networks, and XGBoost.ResultsFour models discovered in GSE113486 had an AUC of 100%, three in GSE113740 with AUC of over 94%, and four in GSE113486 with AUC of over 94%. We identified 10 miRNAs to distinguish ovarian cancer cases from normal controls: hsa-miR-1290, hsa-miR-1233-5p, hsa-miR-1914-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1228-5p, hsa-miR-3184-5p, hsa-miR-6784-5p, hsa-miR-6800-5p, and hsa-miR-5100. Our findings suggest that miRNAs could be used as possible biomarkers for ovarian cancer screening, for possible intervention.
Gene regulatory networks (GRN) are one of the etiologies associated with cancer. Their dysregulation can be associated with cancer formation and asymmetric cellular functions in cancer stem cells, leading to disease persistence and resistance to treatment. Systems that model the complex dynamics of these networks along with adapting to partially known real omics data are closer to reality and may be useful to understand the mechanisms underlying neoplastic phenomena. In this paper, for the first time, modelling of GRNs is performed using delayed nonlinear variable order fractional (VOF) systems in the state space by a new tool called GENAVOS. Although the tool uses gene expression time series data to identify and optimize system parameters, it also models possible epigenetic signals, and the results show that the nonlinear VOF systems have very good flexibility in adapting to real data. We found that GRNs in cancer cells actually have a larger delay parameter than in normal cells. It is also possible to create weak chaotic, periodic, and quasi-periodic oscillations by changing the parameters. Chaos can be associated with the onset of cancer. Our findings indicate a profound effect of time-varying orders on these networks, which may be related to a type of cellular epigenetic memory. By changing the delay parameter and the variable order functions (possible epigenetics signals) for a normal cell system, its behaviour becomes quite similar to the behaviour of a cancer cell. This work confirms the effective role of the miR-17-92 cluster as an epigenetic factor in the cancer cell cycle.
Complex diseases such as cancer are caused by changes in the Gene Regulatory Networks. Systems that model the complex dynamics of these networks along with adapting to real gene expression data are closer to reality and can help understand the creation and treatment of cancer. In this paper, for the first time, modelling of gene regulatory networks is performed using delayed nonlinear variable order fractional systems in the state space by a new tool called GENAVOS. This tool uses gene expression time series data to identify and optimize system parameters. This software has several tools for analyzing system dynamics. The results show that the nonlinear variable order fractional systems have very good flexibility in adapting to real data. We found that regulatory networks in cancer cells actually have a larger delay parameter than in normal cells. It is also possible to create chaos, periodic and quasi-periodic oscillations by changing the delay, degradation and synthesis rates. Our findings indicate a profound effect of time-varying order on these networks, which may be related to a type of cellular memory due to epigenetic and environmental factors. We showed that by changing the delay parameter and the variable order function for a normal cell system, its behavior changes and becomes quite similar to the behavior of a cancer cell. This work also confirms the effective role of the miR-17-92 cluster in the cancer cell cycle. GENAVOS is available at https://github.com/hanif-y/GENAVOS with its user guide and MATLAB codes.
The main part of the noise in digital images arises when taking pictures or transmission. There is noise in the imagescaptured by the image sensors of the real world. Noise, based on its causes can have different probability density functions.For example, such a model is called the Poisson distribution function of the random nature of photon arrival process that isconsistent with the distribution of pixel values measured. The parameters of the noise probability density function (PDF)can be achieved to some extent the properties of the sensor. But, we need to estimate the parameters for imaging settings. Ifwe assume that the PDF of noise is approximately Gaussian, then we need only to estimate the mean and variance becausethe Gaussian PDF with only two parameters is determined. In fact, in many cases, PDF of noise is not Gaussian and it hasunknown distribution. In this study, we introduce a generalized probability density function for modeling noise in imagesand propose a method to estimate its parameters. Because the generalized probability density function has multipleparameters, so use common parameter estimation techniques such as derivative method to maximize the likelihood functionwould be extremely difficult. In this study, we propose the use of evolutionary algorithms for global optimization. Theresults show that this method accurately estimates the probability density function parameters.
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