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ACCOUNTING FOR UNCERTAINTY ABOUT PAST VALUES IN PROBABILISTIC PROJECTIONS OF THE TOTAL FERTILITY RATE FOR MOST COUNTRIES.

ABSTRACT: Since the 1940s, population projections have in most cases been produced using the deterministic cohort component method. However, in 2015, for the first time, in a major advance, the United Nations issued official probabilistic population projections for all countries based on Bayesian hierarchical models for total fertility and life expectancy. The estimates of these models and the resulting projections are conditional on the UN's official estimates of past values. However, these past values are themselves uncertain, particularly for the majority of the world's countries that do not have longstanding high-quality vital registration systems, when they rely on surveys and censuses with their own biases and measurement errors. This paper extends the UN model for projecting future total fertility rates to take account of uncertainty about past values. This is done by adding an additional level to the hierarchical model to represent the multiple data sources, in each case estimating their bias and measurement error variance. We assess the method by out-of-sample predictive validation. While the prediction intervals produced by the extant method (which does not account for this source of uncertainty) have somewhat less than nominal coverage, we find that our proposed method achieves closer to nominal coverage. The prediction intervals become wider for countries for which the estimates of past total fertility rates rely heavily on surveys rather than on vital registration data, especially in high fertility countries.

SUBMITTER: Liu P

PROVIDER: S-EPMC8020736 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: An important step in strain optimization is to identify reactions whose activities should be modified to achieve the desired cellular objective. Preferably, these reactions are identified systematically, as the number of possible combinations of reaction modifications could be very large. Over the last several years, a number of computational methods have been described for identifying combinations of reaction modifications. However, none of these methods explicitly address uncertainties in implementing the reaction activity modifications. In this work, we model the uncertainties as probability distributions in the flux carrying capacities of reactions. Based on this model, we develop an optimization method that identifies reactions for flux capacity modifications to predict outcomes with high statistical likelihood. RESULTS: We compare three optimization methods that select an intervention set comprising up- or down-regulation of reaction flux capacity: CCOpt (Chance constrained optimization), DetOpt (Deterministic optimization), and MCOpt (Monte Carlo-based optimization). We evaluate the methods using a Monte Carlo simulation-based method, MCEval (Monte Carlo Evaluations). We present two case studies analyzing a CHO cell and an adipocyte model. The flux capacity distributions required for our methods were estimated from maximal reaction velocities or elementary mode analysis. The intervention set selected by CCOpt consistently outperforms the intervention set selected by DetOpt in terms of tolerance to flux capacity variations. MCEval shows that the optimal flux predicted based on the CCOpt intervention set is more likely to be obtained, in a probabilistic sense, than the flux predicted by DetOpt. The intervention sets identified by CCOpt and MCOpt were similar; however, the exhaustive sampling required by MCOpt incurred significantly greater computational cost. CONCLUSIONS: Maximizing tolerance to variable engineering outcomes (in modifying enzyme activities) can identify intervention sets that statistically improve the desired cellular objective.

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ACCOUNTING FOR UNCERTAINTY ABOUT PAST VALUES IN PROBABILISTIC PROJECTIONS OF THE TOTAL FERTILITY RATE FOR MOST COUNTRIES.

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