Genetic prediction of quantitative traits: a machine learner's guide focused on height

Machine learning and deep learning have been celebrating many successes in the application to biological problems, especially in the domain of protein folding. Another equally complex and important question has received relatively little attention by the machine learning community, namely the one of prediction of complex traits from genetics. Tackling this problem requires in-depth knowledge of the related genetics literature and awareness of various subtleties associated with genetic data. In this guide, we provide an overview for the machine learning community on current state of the art models and associated subtleties which need to be taken into consideration when developing new models for phenotype prediction. We use height as an example of a continuous-valued phenotype and provide an introduction to benchmark datasets, confounders, feature selection, and common metrics.

Interpretability Aware Model Training to Improve Robustness against Out-of-Distribution Magnetic Resonance Images in Alzheimer's Disease Classification

Owing to its pristine soft-tissue contrast and high resolution, structural magnetic resonance imaging (MRI) is widely applied in neurology, making it a valuable data source for image-based machine learning (ML) and deep learning applications. The physical nature of MRI acquisition and reconstruction, however, causes variations in image intensity, resolution, and signal-to-noise ratio. Since ML models are sensitive to such variations, performance on out-of-distribution data, which is inherent to the setting of a deployed healthcare ML application, typically drops below acceptable levels. We propose an interpretability aware adversarial training regime to improve robustness against out-of-distribution samples originating from different MRI hardware. The approach is applied to 1.5T and 3T MRIs obtained from the Alzheimer's Disease Neuroimaging Initiative database. We present preliminary results showing promising performance on out-of-distribution samples.

Image analysis for Alzheimer's disease prediction: Embracing pathological hallmarks for model architecture design

Alzheimer's disease (AD) is associated with local (e.g. brain tissue atrophy) and global brain changes (loss of cerebral connectivity), which can be detected by high-resolution structural magnetic resonance imaging. Conventionally, these changes and their relation to AD are investigated independently. Here, we introduce a novel, highly-scalable approach that simultaneously captures $\textit{local}$ and $\textit{global}$ changes in the diseased brain. It is based on a neural network architecture that combines patch-based, high-resolution 3D-CNNs with global topological features, evaluating multi-scale brain tissue connectivity. Our local-global approach reached competitive results with an average precision score of $0.95\pm0.03$ for the classification of cognitively normal subjects and AD patients (prevalence $\approx 55\%$).