Background DNA Methylation is one of the most important epigenetic processes that are crucial to regulating the functioning of the human genome without altering the DNA sequence. DNA Methylation data for cancer patients are becoming more accessible than ever, which is attributed to newer DNA sequencing technologies, notably, the relatively low-cost DNA microarray technology by Illumina Infinium. This technology makes it possible to study DNA methylation at hundreds of thousands of different loci. Currently, most of the research found in the literature focuses on the discovery of DNA methylation markers for specific cancer types. A relatively small number of studies have attempted to find unified DNA methylation biomarkers that can diagnose different types of cancer (pan-cancer classification). Results In this study, the aim is to conduct a pan-classification of cancer disease. We retrieved individual data for different types of cancer patients from The Cancer Genome Atlas (TCGA) portal. We selected data for many cancer types: Breast Cancer (BRCA), Ovary Cancer (OV), Stomach Cancer (STOMACH), Colon Cancer (COAD), Kidney Cancer (KIRC), Liver Cancer (LIHC), Lung Cancer (LUSC), Prostate Cancer (PRAD) and Thyroid cancer (THCA). The data was pre-processed and later used to build the required dataset. The system that we developed consists of two main stages. The purpose of the first stage is to perform feature selection and, therefore, decrease the dimensionality of the DNA methylation loci (features). This is accomplished using an unsupervised metaheuristic technique. As for the second stage, we used supervised machine learning and developed deep neural network (DNN) models to help classify the samples’ malignancy status and cancer type. Experimental results showed that compared to recently published methods, our proposed system achieved better classification results in terms of recall, and similar and higher results in terms of precision and accuracy. The proposed system also achieved an excellent receiver operating characteristic area under the curve (ROC AUC) values varying from 0.85 to 0.89. Conclusions This research presented an effective new approach to classify different cancer types based on DNA methylation data retrieved from TCGA. The performance of the proposed system was compared to recently published works, using different performance metrics. It provided better results, confirming the effectiveness of the proposed method for classifying different cancer types based on DNA methylation data.
Epigenetics is the study of phenotypic variations that do not alter DNA sequences. Cancer epigenetics has grown rapidly over the past few years as epigenetic alterations exist in all human cancers. One of these alterations is DNA methylation; an epigenetic process that regulates gene expression and often occurs at tumor suppressor gene loci in cancer. Therefore, studying this methylation process may shed light on different gene functions that cannot otherwise be interpreted using the changes that occur in DNA sequences. Currently, microarray technologies; such as Illumina Infinium BeadChip assays; are used to study DNA methylation at an extremely large number of varying loci. At each DNA methylation site, a beta value (β) is used to reflect the methylation intensity. Therefore, clustering this data from various types of cancers may lead to the discovery of large partitions that can help objectively classify different types of cancers as well as identify the relevant loci without user bias. This study proposed a Nested Big Data Clustering Genetic Algorithm (NBDC-GA); a novel evolutionary metaheuristic technique that can perform cluster-based feature selection based on the DNA methylation sites. The efficacy of the NBDC-GA was tested using real-world data sets retrieved from The Cancer Genome Atlas (TCGA); a cancer genomics program created by the National Cancer Institute (NCI) and the National Human Genome Research Institute. The performance of the NBDC-GA was then compared with that of a recently developed metaheuristic Immuno-Genetic Algorithm (IGA) that was tested using the same data sets. The NBDC-GA outperformed the IGA in terms of convergence performance. Furthermore, the NBDC-GA produced a more robust clustering configuration while simultaneously decreasing the dimensionality of features to a maximum of 67% and of 94.5% for individual cancer type and collective cancer, respectively. The proposed NBDC-GA was also able to identify two chromosomes with highly contrasting DNA methylations activities that were previously linked to cancer.
One of the major culprits that faces Mobile Ad-hoc networks (MANET) is broadcasting, which constitutes a very important part of the infrastructure of such networks. This paper presents a nested genetic algorithm (GA) technique with fuzzy logic-based fitness that optimizes the broadcasting capability of such networks. While normally the optimization of broadcasting is considered as a multi-objective problem with various output parameters that require tuning, the proposed system taps another approach that focuses on a single output parameter, which is the network reachability time. This is the time required for the data to reach a certain percentage of connected clients in the network. The time is optimized by tuning different decision parameters of the Delayed Flooding with Cumulative Neighborhood (DFCN) broadcasting protocol. The proposed system is developed and simulated with the help of the Madhoc network simulator and is applied on different realistic real-life scenarios. The results reveal that the reachability time responds well to the suggested system and shows that each scenario responds differently to the tuning of decision parameters.
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