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  1. Free, publicly-accessible full text available December 1, 2024
  2. Abstract

    Integrative analyses based on statistically relevant associations between genomics and a wealth of intermediary phenotypes (such as imaging) provide vital insights into their clinical relevance in terms of the disease mechanisms. Estimates for uncertainty in the resulting integrative models are however unreliable unless inference accounts for the selection of these associations with accuracy. In this paper, we develop selection-aware Bayesian methods, which (1) counteract the impact of model selection bias through a “selection-aware posterior” in a flexible class of integrative Bayesian models post a selection of promising variables via ℓ1-regularized algorithms; (2) strike an inevitable trade-off between the quality of model selection and inferential power when the same data set is used for both selection and uncertainty estimation. Central to our methodological development, a carefully constructed conditional likelihood function deployed with a reparameterization mapping provides tractable updates when gradient-based Markov chain Monte Carlo (MCMC) sampling is used for estimating uncertainties from the selection-aware posterior. Applying our methods to a radiogenomic analysis, we successfully recover several important gene pathways and estimate uncertainties for their associations with patient survival times.

     
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  3. With only 536 COVID-19 cases and 11 fatalities, India took the historic decision of a 21-day national lockdown on March 25, 2020. The lockdown was first extended to May 3 soon after the analysis of this article was completed, and then to May 18 while this article was being revised. In this article, we use a Bayesian extension of the susceptible-infected-removed (eSIR) model designed for intervention forecasting to study the short- and long-term impact of an initial 21-day lockdown on the total number of COVID-19 infections in India compared to other, less severe nonpharmaceutical interventions. We compare effects of hypothetical durations of lockdown on reducing the number of active and new infections. We find that the lockdown, if implemented correctly, can reduce the total number of cases in the short term, and buy India invaluable time to prepare its health care and disease-monitoring system. Our analysis shows we need to have some measures of suppression in place after the lockdown for increased benefit (as measured by reduction in the number of cases). A longer lockdown from 42–56 days is preferable to substantially ‘flatten the curve’ when compared to 21–28 days of lockdown. Our models focus solely on projecting the number of COVID-19 infections and thus inform policymakers about one aspect of this multifaceted decision-making problem. We conclude with a discussion on the pivotal role of increased testing, reliable and transparent data, proper uncertainty quantification, accurate interpretation of forecasting models, reproducible data science methods, and tools that can enable data-driven policymaking during a pandemic. Our software products are available at covind19.org. 
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