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  1. Abstract

    In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. Our aim is to leverage the advantages of cooperative learning for the computation of polygenic hazard score models via Cox’s proportional hazard model, thereby improving the prediction of the disease-free survival. In our experimental study, we apply our methodology to forecast the disease-free survival for Alzheimer’s disease (AD) using three layers of data. One layer contains epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status and 10 leading principal components. Another layer contains selected genomic loci, and the last layer contains methylation data for selected CpG sites. We demonstrate that the survival curves computed via cooperative learning yield an AUC of around $0.7$, above the state-of-the-art performance of its competitors. Importantly, the proposed methodology returns (1) a linear score that can be easily interpreted (in contrast to machine learning approaches), and (2) a weighting of the predictive power of the involved data layers, allowing for an assessment of the importance of each omic (or other) platform. Similarly to polygenic hazard score models, our methodology also allows one to compute individual survival curves for each patient.

     
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  2. A custom convolutional neural network (CNN) integrated with convolutional long short-term memory (LSTM) achieves accurate 3D (2D + time) segmentation in cross-sectional videos of the Drosophila heart acquired by an optical coherence microscopy (OCM) system. While our previous FlyNet 1.0 model utilized regular CNNs to extract 2D spatial information from individual video frames, convolutional LSTM, FlyNet 2.0, utilizes both spatial and temporal information to improve segmentation performance further. To train and test FlyNet 2.0, we used 100 datasets including 500,000 fly heart OCM images. OCM videos in three developmental stages and two heartbeat situations were segmented achieving an intersection over union (IOU) accuracy of 92%. This increased segmentation accuracy allows morphological and dynamic cardiac parameters to be better quantified.

     
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