De Montfort University
Analysing and predicting differences between methylated and unmethylated DNA sequence features.
Degree: PhD, 2015, De Montfort University
DNA methylation is involved in various biological phenomena, and its dysregulation has been demonstrated as being correlated with a number of human disease processes, including cancers, autism, and autoimmune, mental health and neuro-degenerative ones. It has become important and useful in characterising and modelling these biological phenomena in or-der to understand the mechanism of such occurrences, in relation to both health and disease. An attempt has previously been made to map DNA methylation across human tissues, however, the means of distinguishing between methylated, unmethylated and differentially-methylated groups using DNA sequence features remains unclear. The aim of this study is therefore to: firstly, investigate DNA methylation classes and predict these based on DNA sequence features; secondly, to further identify methylation-associated DNA sequence features, and distinguish methylation differences between males and females in relation to both healthy and diseased, sta-tuses. This research is conducted in relation to three samples within nine biological feature sub-sets extracted from DNA sequence patterns (Human genome database). Two samples contain classes (methylated, unmethy-lated and differentially-methylated) within a total of 642 samples with 3,809 attributes driven from four human chromosomes, i.e. chromosomes 6, 20, 21 and 22, and the third sample contains all human chromosomes, which encompasses 1628 individuals, and then 1,505 CpG loci (features) were extracted by using Hierarchical clustering (a process Heatmap), along with pair correlation distance and then applied feature selection methods. From this analysis, author extract 47 features associated with gender and age, with 17 revealing significant methylation differences between males and females. Methylation classes prediction were applied a K-nearest Neighbour classifier, combined with a ten-fold cross- validation, since to some data were severely imbalanced (i.e., existed in sub-classes), and it has been established that direct analysis in machine-learning is biased towards the majority class. Hence, author propose a Modified- Leave-One-Out (MLOO) cross-validation and AdaBoost methods to tackle these issues, with the aim of compositing a balanced outcome and limiting the bias in-terference from inter-differences of the classes involved, which has provided potential predictive accuracies between 75% and 100%, based on the DNA sequence context.
Subjects/Keywords: 572.8; DNA methylation prediction; CpG islands; DNA feature/pattern; Methylation gender differences; feature subset selection; imbalanced data modelling; ageing and DNA methylation; cancer and DNA methylation
to Zotero / EndNote / Reference
APA (6th Edition):
Ali, I. (2015). Analysing and predicting differences between methylated and unmethylated DNA sequence features. (Doctoral Dissertation). De Montfort University. Retrieved from http://hdl.handle.net/2086/12616
Chicago Manual of Style (16th Edition):
Ali, Isse. “Analysing and predicting differences between methylated and unmethylated DNA sequence features.” 2015. Doctoral Dissertation, De Montfort University. Accessed July 19, 2019.
MLA Handbook (7th Edition):
Ali, Isse. “Analysing and predicting differences between methylated and unmethylated DNA sequence features.” 2015. Web. 19 Jul 2019.
Ali I. Analysing and predicting differences between methylated and unmethylated DNA sequence features. [Internet] [Doctoral dissertation]. De Montfort University; 2015. [cited 2019 Jul 19].
Available from: http://hdl.handle.net/2086/12616.
Council of Science Editors:
Ali I. Analysing and predicting differences between methylated and unmethylated DNA sequence features. [Doctoral Dissertation]. De Montfort University; 2015. Available from: http://hdl.handle.net/2086/12616