Gynaecologists and obstetricians visually interpret cardiotocography (CTG) traces using the International Federation of Gynaecology and Obstetrics (FIGO) guidelines to assess the wellbeing of the foetus during antenatal care. This approach has raised concerns among professionals with regards to inter- and intra-variability where clinical diagnosis only has a 30% positive predictive value when classifying pathological outcomes. Machine learning models, trained with FIGO and other user derived features extracted from CTG traces, have been shown to increase positive predictive capacity and minimise variability. This is only possible however when class distributions are equal which is rarely the case in clinical trials where case-control observations are heavily skewed in favour of normal outcomes. Classes can be balanced using either synthetic data derived from resampled case training data or by decreasing the number of control instances. However, this either introduces bias or removes valuable information. Concerns have also been raised regarding machine learning studies and their reliance on manually handcrafted features. While this has led to some interesting results, deriving an optimal set of features is considered to be an art as well as a science and is often an empirical and time consuming process. In this article, we address both of these issues and propose a novel CTG analysis methodology that a) splits CTG time-series signals into n-size windows with equal class distributions, and b) automatically extracts features from time-series windows using a one dimensional convolutional neural network (1DCNN) and multilayer perceptron (MLP) ensemble. Collectively, the proposed approach normally distributes classes and removes the need to handcrafted features from CTG traces. The 1DCNN-MLP models trained with several windowing strategies are evaluated to determine how well they can distinguish between normal and pathological birth outcomes. Our proposed method achieved good results using a window size of 200 with 80% (95% CI: 75%, 85%) for Sensitivity, 79% (95% CI: 73%, 84%) for Specificity and 86% (95% CI: 81%, 91%) for the Area Under the Curve. The 1DCNN approach is also compared with several traditional machine learning models, which all failed to improve on the windowing 1DCNN strategy proposed.

In this paper, association results from genome-wide association studies (GWAS) are combined with a deep learning framework to test the predictive capacity of statistically significant single nucleotide polymorphism (SNPs) associated with obesity phenotype. Our approach demonstrates the potential of deep learning as a powerful framework for GWAS analysis that can capture information about SNPs and the important interactions between them. Basic statistical methods and techniques for the analysis of genetic SNP data from population-based genome-wide studies have been considered. Statistical association testing between individual SNPs and obesity was conducted under an additive model using logistic regression. Four subsets of loci after quality-control (QC) and association analysis were selected: P-values lower than 1x10-5 (5 SNPs), 1x10-4 (32 SNPs), 1x10-3 (248 SNPs) and 1x10-2 (2465 SNPs). A deep learning classifier is initialised using these sets of SNPs and fine-tuned to classify obese and non-obese observations. Using a deep learning classifier model and genetic variants with P-value < 1x10-2 (2465 SNPs) it was possible to obtain results (SE=0.9604, SP=0.9712, Gini=0.9817, LogLoss=0.1150, AUC=0.9908 and MSE=0.0300). As the P-value increased, an evident deterioration in performance was observed. Results demonstrate that single SNP analysis fails to capture the cumulative effect of less significant variants and their overall contribution to the outcome in disease prediction, which is captured using a deep learning framework.

The aetiology of polygenic obesity is multifactorial, which indicates that life-style and environmental factors may influence multiples genes to aggravate this disorder. Several low-risk single nucleotide polymorphisms (SNPs) have been associated with BMI. However, identified loci only explain a small proportion of the variation ob-served for this phenotype. The linear nature of genome wide association studies (GWAS) used to identify associations between genetic variants and the phenotype have had limited success in explaining the heritability variation of BMI and shown low predictive capacity in classification studies. GWAS ignores the epistatic interactions that less significant variants have on the phenotypic outcome. In this paper we utilise a novel deep learning-based methodology to reduce the high dimensional space in GWAS and find epistatic interactions between SNPs for classification purposes. SNPs were filtered based on the effects associations have with BMI. Since Bonferroni adjustment for multiple testing is highly conservative, an important proportion of SNPs involved in SNP-SNP interactions are ignored. Therefore, only SNPs with p-values < 1x10-2 were considered for subsequent epistasis analysis using stacked auto encoders (SAE). This allows the nonlinearity present in SNP-SNP interactions to be discovered through progressively smaller hidden layer units and to initialise a multi-layer feedforward artificial neural network (ANN) classifier. The classifier is fine-tuned to classify extremely obese and non-obese individuals. The best results were obtained with 2000 compressed units (SE=0.949153, SP=0.933014, Gini=0.949936, Lo-gloss=0.1956, AUC=0.97497 and MSE=0.054057). Using 50 compressed units it was possible to achieve (SE=0.785311, SP=0.799043, Gini=0.703566, Logloss=0.476864, AUC=0.85178 and MSE=0.156315).