Conditional frequency spectra as a tool for studying selection on complex traits in biobanks.

Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of frequency and effect size - but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. To account for GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort. Before considering these conditional frequency spectra, we first characterized the impact of selection and non-equilibrium demography on allele frequency dynamics forwards and backwards in time. We then used these results to understand conditional frequency spectra under realistic human demography. Finally, we investigated empirical conditional frequency spectra for GWAS variants associated with 106 complex traits, finding compelling evidence for either stabilizing or purifying selection. Our results provide insight into polygenic score portability and other properties of variants ascertained with GWAS, highlighting the utility of conditional frequency spectra.

AIoT Used for COVID-19 Pandemic Prevention and Control.

The pandemic of COVID-19 is continuing to wreak havoc in 2021, with at least 170 million victims around the world. Healthcare systems are overwhelmed by the large-scale virus infection. Luckily, Internet of Things (IoT) is one of the most effective paradigms in the intelligent world, in which the technology of artificial intelligence (AI), like cloud computing and big data analysis, is playing a vital role in preventing the spread of the pandemic of COVID-19. AI and 5G technologies are advancing by leaps and bounds, further strengthening the intelligence and connectivity of IoT applications, and conventional IoT has been gradually upgraded to be more powerful AI + IoT (AIoT). For example, in terms of remote screening and diagnosis of COVID-19 patients, AI technology based on machine learning and deep learning has recently upgraded medical equipment significantly and has reshaped the workflow with minimal contact with patients, so medical specialists can make clinical decisions more efficiently, providing the best protection not only to patients but also to specialists themselves. This paper reviews the latest progress made in combating COVID-19 with both IoT and AI and also provides comprehensive details on how to combat the pandemic of COVID-19 as well as the technologies that may be applied in the future.

Fitness Estimation for Viral Variants in the Context of Cellular Coinfection.

Animal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host's infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.