Genomic predictions under different genetic architectures are impacted by mating designs.

Mating in animal communities must be managed in a way that assures the performance increase in the progenies without increasing the rate of inbreeding. It has currently become possible to identify millions of single nucleotide polymorphisms (SNPs), and it is feasible to select animals based on genome-wide marker profiles. This study aimed to evaluate the impact of five mating designs among individuals (random, positive and negative assortative, minimized and maximized inbreeding) on genomic prediction accuracy. The choice of these five particular mating designs provides a thorough analysis of the way genetic diversity, relatedness, inbreeding, and biological conditions influence the accuracy of genomic predictions. Utilizing a stochastic simulation technique, various marker and quantitative trait loci (QTL) densities were taken into account. The heritabilities of a simulated trait were 0.05, 0.30, and 0.60. A validation population that only had genotypic records was taken into consideration, and a reference population that had both genotypic and phenotypic records was considered for every simulation scenario. By measuring the correlation between estimated and true breeding values, the prediction accuracy was calculated. Computing the regression of true genomic breeding value on estimated genomic breeding value allowed for the examination of prediction bias. The scenario with a positive assortative mating design had the highest accuracy of genomic prediction (0.733 ± 0.003 to 0.966 ± 0.001). In a case of negative assortative mating, the genomic evaluation's accuracy was lowest (0.680 ± 0.011 to 0.899 ± 0.003). Applying the positive assortative mating design resulted in the unbiased regression coefficients of true genomic breeding value on estimated genomic breeding value. Based on the current results, it is suggested to implement positive assortative mating in genomic evaluation programs to obtain unbiased genomic predictions with greater accuracy. This study implies that animal breeding programs can improve offspring performance without compromising genetic health by carefully managing mating strategies based on genetic diversity, relatedness, and inbreeding levels. To maximize breeding results and ensure long-term genetic improvement in animal populations, this study highlights the importance of considering different mating designs when evaluating genomic information. When incorporating positive assortative mating or other mating schemes into genomic evaluation programs, it is critical to consider the complex relationship between gene interactions, environmental influences, and genetic drift to ensure the stability and effectiveness of breeding efforts. Further research and comprehensive analyzes are needed to fully understand the impact of these factors and their possible complex interactions on the accuracy of genomic prediction and to develop strategies that optimize breeding outcomes in animal populations.

Supporting equitable and responsible highway safety improvement funding allocation strategies - Why AI prediction biases matter.

The existing methodologies for allocating highway safety improvement funding closely rely on the utilization of crash prediction models. Specifically, these models produce predictions that estimate future crash hazard levels in different geographical areas, which subsequently support the future funding allocation strategies. In recent years, there is a burgeoning interest in applying artificial intelligence (AI)-based models to perform crash prediction tasks. Despite the remarkable accuracy of these AI-based crash prediction models, they have been observed to yield biased prediction outcomes across areas of different socioeconomic statuses. These biases are primarily attributed to the inherent measurement and representation biases of AI-based prediction models. More precisely, measurement bias arises from the selection of target variables to reflect crash hazard levels, while representation bias results from the issue of imbalanced number of samples representing areas with different socioeconomic statuses within the dataset. Consequently, these biased prediction outcomes have the potential to perpetuate an unfair allocation of funding resources, contributing to worsen social inequality over time. Drawing upon a real-world case study in North Carolina, this study designs an AI-based crash prediction model that utilizes previous sociodemographic and crash-related variables to predict future severe crash rate of each area to reflect the crash hazardous level. By incorporating a fair regression framework, this study endeavors to transform the crash prediction model to become both fair and accurate, aiming to support equitable and responsible safety improvement funding allocation strategies.

Analysis of SARS-CoV-2 in wastewater for prevalence estimation and investigating clinical diagnostic test biases.

Here we analyze SARS-CoV-2 genome copies in Catalonia's wastewater during the Omicron peak and develop a mathematical model to estimate the number of infections and the temporal relationship between reported and unreported cases. 1-liter samples from 16 wastewater treatment plants were collected and used in a compartmental epidemiological model. The average correlation between genome copies and reported cases was 0.85, with an average delay of 8.8 days. The model estimated that 53% of the population was infected, compared to the 19% reported cases. The under-reporting was highest in November and December 2021. The maximum genome copies shed in feces by an infected individual was estimated to range from 1.4×108 gc/g to 4.4×108 gc/g. Our framework demonstrates the potential of wastewater data as a leading indicator for daily new infections, particularly in contexts with low detection rates. It also serves as a complementary tool for prevalence estimation and offers a general approach for integrating wastewater data into compartmental models.

Impact and utility of shallow pedigree using single-step genomic BLUP for prediction of unbiased genomic breeding values.

In unstructured dairy programs, pedigree is usually shallow, which leads to biased prediction of breeding values using best linear unbiased prediction (BLUP). The objective of this study was to come out with a genomic prediction strategy that can utilize shallow pedigree information and predict unbiased and more accurate GEBV for sex-limited traits in a small population using single-step GBLUP (ssGBLUP). The data and models for a population under selection were simulated. Out of current 10 generations, 10th generation with 1000 candidates served as validation population. For the complete pedigree scenario, pedigree (P)BLUP estimated breeding values (EBV) were unbiased with accuracy (r) of 0.35 ± 0.02 and 0.26 ± 0.01 for 0.3 and 0.1 h2 scenario, respectively. For the shallow pedigree, biased prediction of breeding values and low accuracies were obtained with linear decline in the accuracy of EBV for removal of information on more distant pedigree. Accuracy and bias (ρ) for scenario with removing 4 distant generations from pedigree were 0.30 ± 0.02 and 0.55 ± 0.03, respectively, in moderate h2 scenario. Use of Genomic (G)BLUP, especially with "extreme phenotypic contrast selective genotyping," (TB) resulted in higher accuracy for a small reference of females; however, GEBV were highly biased. We observed that ssGBLUPF, where the numerator relationship matrix is corrected for inbreeding, resulted in more accurate and unbiased estimates of GEBV across shallow pedigree scenario, with TB all female reference (missing 4 distant generations: r = 0.50 ± 0.02; ρ = 0.96 ± 0.02). We recommend use of ssGBLUPF with two tailed selectively genotyped all female reference in shallow pedigree scenarios, to obtain unbiased and accurate GEBV for sex-limited traits, when resources are limited.

Accuracy of genomic selection for reducing susceptibility to pendulous crop in turkey (Meleagris gallopavo).

Pendulous crop (PC) in the turkey occurs when the crop distends from its normal position, thereby preventing the movement of feed and water from the crop down into the digestive system. This condition negatively impacts the turkey industry at both production and welfare levels. In this study, we estimated the genetic parameters for PC incidence and its genetic correlation with 5 production traits. Additionally, we evaluated the prediction accuracy and bias of breeding values for the selection candidates using pedigree (BLUP) or pedigree-genomic (ssGBLUP) relationships among the animals. A total of 245,783 turkey records were made available by Hybrid Turkeys, Kitchener, Canada. Of these, 6,545 were affected with PC. In addition, the data included 9,634 records for breast meat yield (BMY); 5,592 records for feed conversion ratio (FCR) and residual feed intake (RFI) in males; 170,844 records for body weight (BW) and walking score (WS) between 18 and 20 wk of age for males (71,012) and females (99,832), respectively. Among this population, 36,830 were genotyped using a 65K SNP Illumina Inc. chip. While all animals passed the quality control criteria, only 53,455 SNP markers were retained for subsequent analysis. Heritability for PC was estimated at 0.16 ± 0.00 and 0.17 ± 0.00 using BLUP and ssGBLUP, respectively. The incidence of PC was not genetically correlated with WS or FCR. Low unfavourable genetic correlations with BW (0.12 and 0.14), BMY (0.24 and 0.24) and RFI (-0.33 and -0.28) were obtained using BLUP and ssGBLUP, respectively. Using ssGBLUP showed higher prediction accuracy (0.51) for the breeding values for the selection candidates than the pedigree-based model (0.35). Whereas the bias of the prediction was slightly reduced with ssGBLUP (0.33 ± 0.05) than BLUP (0.30 ± 0.08), both models showed a regression coefficient lower than one, indicating inflation in the predictions. The results of this study suggest that PC is a heritable trait and selection for lower PC incidence rates is feasible. Although further investigation is necessary, selection for BW, BMY, and RFI may increase PC incidence. Incorporating genomic information would lead to higher accuracy in predicting the genetic merit for selection candidates.

The development and deployment of a model for hospital-level COVID-19 associated patient demand intervals from consistent estimators (DICE).

Hospitals commonly project demand for their services by combining their historical share of regional demand with forecasts of total regional demand. Hospital-specific forecasts of demand that provide prediction intervals, rather than point estimates, may facilitate better managerial decisions, especially when demand overage and underage are associated with high, asymmetric costs. Regional point forecasts of patient demand are commonly available, e.g., for the number of people requiring hospitalization due to an epidemic such as COVID-19. However, even in this common setting, no probabilistic, consistent, computationally tractable forecast is available for the fraction of patients in a region that a particular institution should expect. We introduce such a forecast, DICE (Demand Intervals from Consistent Estimators). We describe its development and deployment at an academic medical center in California during the 'second wave' of COVID-19 in the Unite States. We show that DICE is consistent under mild assumptions and suitable for use with perfect, biased and unbiased regional forecasts. We evaluate its performance on empirical data from a large academic medical center as well as on synthetic data.

Effect of selection and selective genotyping for creation of reference on bias and accuracy of genomic prediction.

Reference populations for genomic selection usually involve selected individuals, which may result in biased prediction of estimated genomic breeding values (GEBV). In a simulation study, bias and accuracy of GEBV were explored for various genetic models with individuals selectively genotyped in a typical nucleus breeding program. We compared the performance of three existing methods, that is, Best Linear Unbiased Prediction of breeding values using pedigree-based relationships (PBLUP), genomic relationships for genotyped animals only (GBLUP) and a Single-Step approach (SSGBLUP) using both. For a scenario with no-selection and random mating (RR), prediction was unbiased. However, lower accuracy and bias were observed for scenarios with selection and random mating (SR) or selection and positive assortative mating (SA). As expected, bias disappeared when all individuals were genotyped and used in GBLUP. SSGBLUP showed higher accuracy compared to GBLUP, and bias of prediction was negligible with SR. However, PBLUP and SSGBLUP still showed bias in SA due to high inbreeding. SSGBLUP and PBLUP were unbiased provided that inbreeding was accounted for in the relationship matrices. Selective genotyping based on extreme phenotypic contrasts increased the prediction accuracy, but prediction was biased when using GBLUP. SSGBLUP could correct the biasedness while gaining higher accuracy than GBLUP. In a typical animal breeding program, where it is too expensive to genotype all animals, it would be appropriate to genotype phenotypically contrasting selection candidates and use a Single-Step approach to obtain accurate and unbiased prediction of GEBV.

Model-Based Conditional Weighted Residuals Analysis for Structural Model Assessment.

Nonlinear mixed effects models are widely used to describe longitudinal data to improve the efficiency of drug development process or increase the understanding of the studied disease. In such settings, the appropriateness of the modeling assumptions is critical in order to draw correct conclusions and must be carefully assessed for any substantial violations. Here, we propose a new method for structure model assessment, based on assessment of bias in conditional weighted residuals (CWRES). We illustrate this method by assessing prediction bias in two integrated models for glucose homeostasis, the integrated glucose-insulin (IGI) model, and the integrated minimal model (IMM). One dataset was simulated from each model then analyzed with the two models. CWRES outputted from each model fitting were modeled to capture systematic trends in CWRES as well as the magnitude of structural model misspecifications in terms of difference in objective function values (ΔOFVBias). The estimates of CWRES bias were used to calculate the corresponding bias in conditional predictions by the inversion of first-order conditional estimation method's covariance equation. Time, glucose, and insulin concentration predictions were the investigated independent variables. The new method identified correctly the bias in glucose sub-model of the integrated minimal model (IMM), when this bias occurred, and calculated the absolute and proportional magnitude of the resulting bias. CWRES bias versus the independent variables agreed well with the true trends of misspecification. This method is fast easily automated diagnostic tool for model development/evaluation process, and it is already implemented as part of the Perl-speaks-NONMEM software.

Knowledge of Previous Tasks: Task Similarity Influences Bias in Task Duration Predictions.

Bias in predictions of task duration has been attributed to misremembering previous task duration and using previous task duration as a basis for predictions. This research sought to further examine how previous task information affects prediction bias by manipulating task similarity and assessing the role of previous task duration feedback. Task similarity was examined through participants performing two tasks 1 week apart that were the same or different. Duration feedback was provided to all participants (Experiment 1), its recall was manipulated (Experiment 2), and its provision was manipulated (Experiment 3). In all experiments, task similarity influenced bias on the second task, with predictions being less biased when the first task was the same task. However, duration feedback did not influence bias. The findings highlight the pivotal role of knowledge about previous tasks in task duration prediction and are discussed in relation to the theoretical accounts of task duration prediction bias.

Effect of genotyped cows in the reference population on the genomic evaluation of Holstein cattle.

This study evaluated the dependence of reliability and prediction bias on the prediction method, the contribution of including animals (bulls or cows), and the genetic relatedness, when including genotyped cows in the progeny-tested bull reference population. We performed genomic evaluation using a Japanese Holstein population, and assessed the accuracy of genomic enhanced breeding value (GEBV) for three production traits and 13 linear conformation traits. A total of 4564 animals for production traits and 4172 animals for conformation traits were genotyped using Illumina BovineSNP50 array. Single- and multi-step methods were compared for predicting GEBV in genotyped bull-only and genotyped bull-cow reference populations. No large differences in realized reliability and regression coefficient were found between the two reference populations; however, a slight difference was found between the two methods for production traits. The accuracy of GEBV determined by single-step method increased slightly when genotyped cows were included in the bull reference population, but decreased slightly by multi-step method. A validation study was used to evaluate the accuracy of GEBV when 800 additional genotyped bulls (POPbull) or cows (POPcow) were included in the base reference population composed of 2000 genotyped bulls. The realized reliabilities of POPbull were higher than those of POPcow for all traits. For the gain of realized reliability over the base reference population, the average ratios of POPbull gain to POPcow gain for production traits and conformation traits were 2.6 and 7.2, respectively, and the ratios depended on heritabilities of the traits. For regression coefficient, no large differences were found between the results for POPbull and POPcow. Another validation study was performed to investigate the effect of genetic relatedness between cows and bulls in the reference and test populations. The effect of genetic relationship among bulls in the reference population was also assessed. The results showed that it is important to account for relatedness among bulls in the reference population. Our studies indicate that the prediction method, the contribution ratio of including animals, and genetic relatedness could affect the prediction accuracy in genomic evaluation of Holstein cattle, when including genotyped cows in the reference population.