Exploring the application of deep learning methods for polygenic risk score estimation

BackgroundPolygenic risk scores (PRS) summarise genetic information into a single number with multiple clinical and research uses. Machine learning (ML) has revolutionised a diverse set of fields, however, the impact of ML on genomics in general, and PRSs in particular, has been less significant. We explore how ML can improve the generation of PRSs. MethodsWe train ML models on known PRSs using UK Biobank data. We explore whether the models can recreate human programmed PRSs, including using a single model to generate multiple PRSs, and the difficulty in using ML for PRS generation. We also investigate how ML can compensate for missing data and the constraints on performance. ResultsWe demonstrate almost perfect generation of PRSs, including when using one model to predict multiple scores, and with little loss of performance with reduced quantity of training data. For an example set of missing SNPs the MLP produces predictions that enable separation of cases from population samples with an area under the receiver operating characteristic curve of 0.847 (95% CI: 0.828-0.864) compared to 0.798 (95% CI: 0.779-0.818) for the PRS. We provide evidence that input information is the limiting factor of further improvement. ConclusionsML can accurately generate PRSs, including with one model for multiple PRSs. The models are transferable and have high longevity. With certain missing SNPs the ML models can statistically significantly improve on normal PRS generation. Models trained are probably at the edge of performance and further improvements likely require use of additional input data. Code is available at https://github.com/stevensquires/