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Background Many traits and diseases are thought to be driven by >1 gene (polygenic). Polygenic risk scores (PRS) hence expand on genome-wide association studies by taking multiple genes into account when risk models are built. However, PRS only considers the additive effect of individual genes but not epistatic interactions or the combination of individual and interacting drivers. While evidence of epistatic interactions ais found in small datasets, large datasets have not been processed yet owing to the high computational complexity of the search for epistatic interactions. Findings We have developed VariantSpark, a distributed machine learning framework able to perform association analysis for complex phenotypes that are polygenic and potentially involve a large number of epistatic interactions. Efficient multi-layer parallelization allows VariantSpark to scale to the whole genome of population-scale datasets with 100,000,000 genomic variants and 100,000 samples. Conclusions Compared with traditional monogenic genome-wide association studies, VariantSpark better identifies genomic variants associated with complex phenotypes. VariantSpark is 3.6 times faster than ReForeSt and the only method able to scale to ultra-high-dimensional genomic data in a manageable time. [ABSTRACT FROM AUTHOR]

Pre‐clinical responses to fast‐moving infectious disease outbreaks heavily depend on choosing the best isolates for animal models that inform diagnostics, vaccines and treatments. Current approaches are driven by practical considerations (e.g. first available virus isolate) rather than a detailed analysis of the characteristics of the virus strain chosen, which can lead to animal models that are not representative of the circulating or emerging clusters. Here, we suggest a combination of epidemiological, experimental and bioinformatic considerations when choosing virus strains for animal model generation. We discuss the currently chosen SARS‐CoV‐2 strains for international coronavirus disease (COVID‐19) models in the context of their phylogeny as well as in a novel alignment‐free bioinformatic approach. Unlike phylogenetic trees, which focus on individual shared mutations, this new approach assesses genome‐wide co‐developing functionalities and hence offers a more fluid view of the 'cloud of variances' that RNA viruses are prone to accumulate. This joint approach concludes that while the current animal models cover the existing viral strains adequately, there is substantial evolutionary activity that is likely not considered by the current models. Based on insights from the non‐discrete alignment‐free approach and experimental observations, we suggest isolates for future animal models. [ABSTRACT FROM AUTHOR]

Lifespan and fecundity, the main components in evolutionary fitness, are both strongly affected by nutritional state. Geometric framework of nutrition (GFN) experiments has shown that lifespan and fecundity are separated in nutrient space leading to a functional trade-off between the two traits. Here we develop a spatially explicit agent-based model (ABM) using the GFN to explore how ecological factors may cause selection on macronutrient appetites to optimally balance these life-history traits. We show that increasing the risk of extrinsic mortality favours intake of a mixture of nutrients that is associated with maximal fecundity at the expense of reduced longevity and that this result is robust across spatial and nutritional environments. These model behaviours are consistent with what has been observed in studies that quantify changes in life history in response to environmental manipulations. Previous GFN-derived ABMs have treated fitness as a single value. This is the first such model to instead decompose fitness into its primary component traits, longevity and fecundity, allowing evolutionary fitness to be an emergent property of the two. Our model demonstrates that selection on macronutrient appetites may affect life-history trade-offs and makes predictions that can be directly tested in artificial selection experiments.