RESUMEN
BackgroundEthnically diverse and socio-economically deprived communities have been differentially affected by the COVID-19 pandemic in the UK. MethodUsing a multilevel regression model we assess the time-varying association between SARS-CoV-2 infections and areal level deprivation and ethnicity. We separately consider weekly test positivity rate (number of positive tests over the total number of tests) and estimated unbiased prevalence (proportion of individuals in the population who would test positive) at the Lower Tier Local Authority (LTLA) level. The model also adjusts for age, urbanicity, vaccine uptake and spatio-temporal correlation structure. FindingsComparing the least deprived and predominantly White areas with most deprived and predominantly non-White areas over the whole study period, the weekly positivity rate increases by 13% from 2{middle dot}97% to 3{middle dot}35%. Similarly, prevalence increases by 10% from 0{middle dot}37% to 0{middle dot}41%. Deprivation has a stronger effect until October 2020, while the effect of ethnicity becomes slightly more pronounced at the peak of the second wave and then again in May-June 2021. Not all BAME groups were equally affected: in the second wave of the pandemic, LTLAs with large South Asian populations were the most affected, whereas areas with large Black populations did not show increased values for either outcome during the entire period under analysis. InterpretationAt the area level, IMD and BAME% are both associated with an increased COVID-19 burden in terms of prevalence (disease spread) and test positivity (disease monitoring), and the strength of association varies over the course of the pandemic. The consistency of results across the two outcome measures suggests that community level characteristics such as deprivation and ethnicity have a differential impact on disease exposure or susceptibility rather than testing access and habits. FundingsEPSRC, MRC, The Alan Turing Institute, NIH, UKHSA, DHSC, NIHR
RESUMEN
Targeted surveillance testing schemes for SARS-CoV-2 focus on certain subsets of the population, such as individuals experiencing one or more of a prescribed list of symptoms. These schemes have routinely been used to monitor the spread of SARS-CoV-2 in countries across the world. The number of positive tests in a given region can provide local insights into important epidemiological parameters, such as prevalence and effective reproduction number. Moreover, targeted testing data has been used inform the deployment of localised non-pharmaceutical interventions. However, surveillance schemes typically suffer from ascertainment bias; the individuals who are tested are not necessarily representative of the wider population of interest. Here, we show that data from randomised testing schemes, such as the REACT study in the UK, can be used to debias fine-scale targeted testing data in order to provide accurate localised estimates of the number of infectious individuals. We develop a novel, integrative causal framework that explicitly models the process underlying the selection of individuals for targeted testing. The output from our model can readily be incorporated into longitudinal analyses to provide local estimates of the reproduction number. We apply our model to characterise the size of the infectious population in England between June 2020 and January 2021. Our local estimates of the effective reproduction number are predictive of future changes in positive case numbers. We also capture local increases in both prevalence and effective reproductive number in the South East from November 2020 to December 2020, reflecting the spread of the Kent variant. Our results illustrate the complementary roles of randomised and targeted testing schemes. Preparations for future epidemics should ensure the rapid deployment of both types of schemes to accurately monitor the spread of emerging and ongoing infectious diseases.
RESUMEN
Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.