Overview of the use of genomic data in animal breeding / Panorama do uso de dados genômicos no melhoramento genético animal

The use of molecular information in breeding programs contributed to important advances in the improvement of traits of economic interest in livestock production. The advent of single nucleotide polymorphism (SNP) panels applied to genome-wide selection (GWS) and genome-wide association studies (GWAS), along with computational advances (e.g., use of powerful software and robust analyses) allowed a better understanding of the genetic architecture of farm animals and increased the selection efficiency. In this context, the statistic method single-step GBLUP has been frequently used to perform GWS, and more recently GWAS analyses, providing accurate predictions and QTL detection, respectively. Nevertheless, in developing countries, species such as sheep and goats, whose genomic data are more difficult to be obtained, the use of data simulation has been efficient in the study of the major factors involved in the selection process, such as size of training population, density of SNP chips, and genotyping strategies. The effects of these factors are directly associated with the prediction accuracy of genomic breeding values. In this review we showed important aspects of the use of genomics in the genetic improvement of production traits of animals, the main methods currently used for prediction and estimation of molecular marker effects, the importance of data simulation for validation of those methods, as well as the advantages, challenges and limitations of the use of GWS and GWAS in the current scenario of livestock production.

Em programas de melhoramento genético, o uso de informações moleculares garantiu importantes avanços para a melhoria de características de interesse econômico, no âmbito da produção animal. O advento da tecnologia de painéis de SNPs aplicados à seleção genômica ampla (GWS) e associação genômica ampla (GWAS), aliado ao avanço computacional, com o uso de softwares e análises robustas, permitiram melhor compreensão sobre a arquitetura genética dos animais de produção e, consequentemente, maior eficiência na seleção. Nesse contexto, o método estatístico single-step GBLUP tem sido utilizado, frequentemente, na execução da GWS e, mais recentemente, em GWAS, possibilitando predições acuradas e detecção de QTLs, respectivamente. No entanto, em países em desenvolvimento e, em espécies como os ovinos e caprinos, que existe maior dificuldade para a aquisição de dados genômicos, o uso da simulação de dados tem se mostrado eficiente para estudar os principais fatores envolvidos no processo de seleção, como o tamanho da população de treinamento, densidade de chipde SNPs e estratégias de genotipagem, cujos efeitos estão diretamente associados à acurácia da predição de valores genéticos genômicos. Nesta revisão, serão abordados pontos importantes sobre o uso da genômica no melhoramento genético de características produtivas em animais, principais métodos de predição e estimação de efeitos de marcadores moleculares na atualidade, a importância da simulação de dados para a validação desses métodos, bem como as vantagens, os desafios e as limitações no cenário atual da produção animal com o uso da seleção e associação genômica ampla.

Overview of the use of genomic data in animal breeding / Panorama do uso de dados genômicos no melhoramento genético animal

ABSTRACT: The use of molecular information in breeding programs contributed to important advances in the improvement of traits of economic interest in livestock production. The advent of single nucleotide polymorphism (SNP) panels applied to genome-wide selection (GWS) and genome-wide association studies (GWAS), along with computational advances (e.g., use of powerful software and robust analyses) allowed a better understanding of the genetic architecture of farm animals and increased the selection efficiency. In this context, the statistic method single-step GBLUP has been frequently used to perform GWS, and more recently GWAS analyses, providing accurate predictions and QTL detection, respectively. Nevertheless, in developing countries, species such as sheep and goats, whose genomic data are more difficult to be obtained, the use of data simulation has been efficient in the study of the major factors involved in the selection process, such as size of training population, density of SNP chips, and genotyping strategies. The effects of these factors are directly associated with the prediction accuracy of genomic breeding values. In this review we showed important aspects of the use of genomics in the genetic improvement of production traits of animals, the main methods currently used for prediction and estimation of molecular marker effects, the importance of data simulation for validation of those methods, as well as the advantages, challenges and limitations of the use of GWS and GWAS in the current scenario of livestock production.

RESUMO: Em programas de melhoramento genético, o uso de informações moleculares garantiu importantes avanços para a melhoria de características de interesse econômico, no âmbito da produção animal. O advento da tecnologia de painéis de SNPs aplicados à seleção genômica ampla (GWS) e associação genômica ampla (GWAS), aliado ao avanço computacional, com o uso de softwares e análises robustas, permitiram melhor compreensão sobre a arquitetura genética dos animais de produção e, consequentemente, maior eficiência na seleção. Nesse contexto, o método estatístico single-step GBLUP tem sido utilizado, frequentemente, na execução da GWS e, mais recentemente, em GWAS, possibilitando predições acuradas e detecção de QTLs, respectivamente. No entanto, em países em desenvolvimento e, em espécies como os ovinos e caprinos, que existe maior dificuldade para a aquisição de dados genômicos, o uso da simulação de dados tem se mostrado eficiente para estudar os principais fatores envolvidos no processo de seleção, como o tamanho da população de treinamento, densidade de chipde SNPs e estratégias de genotipagem, cujos efeitos estão diretamente associados à acurácia da predição de valores genéticos genômicos. Nesta revisão, serão abordados pontos importantes sobre o uso da genômica no melhoramento genético de características produtivas em animais, principais métodos de predição e estimação de efeitos de marcadores moleculares na atualidade, a importância da simulação de dados para a validação desses métodos, bem como as vantagens, os desafios e as limitações no cenário atual da produção animal com o uso da seleção e associação genômica ampla.

Predicting Activity Duration in Smart Sensing Environments Using Synthetic Data and Partial Least Squares Regression: The Case of Dementia Patients.

The accurate recognition of activities is fundamental for following up on the health progress of people with dementia (PwD), thereby supporting subsequent diagnosis and treatments. When monitoring the activities of daily living (ADLs), it is feasible to detect behaviour patterns, parse out the disease evolution, and consequently provide effective and timely assistance. However, this task is affected by uncertainties derived from the differences in smart home configurations and the way in which each person undertakes the ADLs. One adjacent pathway is to train a supervised classification algorithm using large-sized datasets; nonetheless, obtaining real-world data is costly and characterized by a challenging recruiting research process. The resulting activity data is then small and may not capture each person's intrinsic properties. Simulation approaches have risen as an alternative efficient choice, but synthetic data can be significantly dissimilar compared to real data. Hence, this paper proposes the application of Partial Least Squares Regression (PLSR) to approximate the real activity duration of various ADLs based on synthetic observations. First, the real activity duration of each ADL is initially contrasted with the one derived from an intelligent environment simulator. Following this, different PLSR models were evaluated for estimating real activity duration based on synthetic variables. A case study including eight ADLs was considered to validate the proposed approach. The results revealed that simulated and real observations are significantly different in some ADLs (p-value < 0.05), nevertheless synthetic variables can be further modified to predict the real activity duration with high accuracy (R2(pred)>90%).

Anomaly Identification during Polymerase Chain Reaction for Detecting SARS-CoV-2 Using Artificial Intelligence Trained from Simulated Data.

Real-time reverse transcription (RT) PCR is the gold standard for detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), owing to its sensitivity and specificity, thereby meeting the demand for the rising number of cases. The scarcity of trained molecular biologists for analyzing PCR results makes data verification a challenge. Artificial intelligence (AI) was designed to ease verification, by detecting atypical profiles in PCR curves caused by contamination or artifacts. Four classes of simulated real-time RT-PCR curves were generated, namely, positive, early, no, and abnormal amplifications. Machine learning (ML) models were generated and tested using small amounts of data from each class. The best model was used for classifying the big data obtained by the Virology Laboratory of Simon Bolivar University from real-time RT-PCR curves for SARS-CoV-2, and the model was retrained and implemented in a software that correlated patient data with test and AI diagnoses. The best strategy for AI included a binary classification model, which was generated from simulated data, where data analyzed by the first model were classified as either positive or negative and abnormal. To differentiate between negative and abnormal, the data were reevaluated using the second model. In the first model, the data required preanalysis through a combination of prepossessing. The early amplification class was eliminated from the models because the numbers of cases in big data was negligible. ML models can be created from simulated data using minimum available information. During analysis, changes or variations can be incorporated by generating simulated data, avoiding the incorporation of large amounts of experimental data encompassing all possible changes. For diagnosing SARS-CoV-2, this type of AI is critical for optimizing PCR tests because it enables rapid diagnosis and reduces false positives. Our method can also be used for other types of molecular analyses.

Non-invasive method to analyse the risk of developing diabetic foot.

Foot complications (diabetic foot) are among the most serious and costly complications of diabetes mellitus. Amputation of all or part of a lower extremity is usually preceded by a foot ulcer. To prevent diabetic foot, an automatic non-invasive method to identify patients with diabetes who have a high risk of developing diabetic foot is proposed. To design the proposed method, information concerning social scope and self-care of 153 diabetic patients was presented to the K-means clustering algorithm, which divided the data into two groups: high risk and low risk of developing diabetic foot. In the operational stage, the Euclidian distance from the information vector to the centroids of each group of risk is used as criterion for classification. Both real and simulated data were used to evaluate the method in which promising results were achieved with accuracy of 0.97 ± 0.06 for simulated data and 0.68 ± 0.16 considering the classification of specialists as the gold standard for real data. The method requires a simple computational processing and can be useful for basic health units to triage diabetic patients helping the health-care team to reduce the number of cases of diabetic foot.

Inferência Bayesiana na análise genética de populações diplóides: estimação do coeficiente de endogamia e da taxa de fecundação cruzada / Bayesian inference in genetic analysis of diploid populations: inbreeding coefficient and outcrossing rate estimation

Neste estudo, utilizou-se a metodologia Bayesiana para estimar o coeficiente de endogamia e a taxa de fecundação cruzada de uma população diplóide por meio do modelo aleatório de COCKERHAM para freqüências alélicas. Um sistema de simulação de dados foi estruturado para validar a metodologia utilizada. O algoritmo Gibbs Sampler foi implementado no software R para obter amostras das distribuições marginais a posteriori para o coeficiente de endogamia e para a taxa de fecundação. O método Bayesiano mostrou-se eficiente na estimação dos parâmetros, pois os valores paramétricos utilizados na simulação encontravam-se dentro do intervalo de credibilidade de 95 por cento em todos os cenários considerados. A convergência do algoritmo Gibbs Sampler foi verificada, validando assim os resultados obtidos.

The Bayesian methodology was used to estimate the inbreeding coefficient and outcrossing rate in diploid populations by COCKERHAM random model to allelic frequency. The proposed methodology was evaluated by data simulation. The Gibbs Sampler algorithm was implemented in the R statistical software to obtain the random samples of the inbreeding coefficient and outcrossing rate posteriors marginal distributions. The Bayesian method showed good results, because the 95 percent credible intervals contained the true parameter values to all of the selected scenes. The Gibbs Sampler convergence was checked and this validated the estimation results.

Inferência Bayesiana na análise genética de populações diplóides: estimação do coeficiente de endogamia e da taxa de fecundação cruzada / Bayesian inference in genetic analysis of diploid populations: inbreeding coefficient and outcrossing rate estimation

Neste estudo, utilizou-se a metodologia Bayesiana para estimar o coeficiente de endogamia e a taxa de fecundação cruzada de uma população diplóide por meio do modelo aleatório de COCKERHAM para freqüências alélicas. Um sistema de simulação de dados foi estruturado para validar a metodologia utilizada. O algoritmo Gibbs Sampler foi implementado no software R para obter amostras das distribuições marginais a posteriori para o coeficiente de endogamia e para a taxa de fecundação. O método Bayesiano mostrou-se eficiente na estimação dos parâmetros, pois os valores paramétricos utilizados na simulação encontravam-se dentro do intervalo de credibilidade de 95 por cento em todos os cenários considerados. A convergência do algoritmo Gibbs Sampler foi verificada, validando assim os resultados obtidos.(AU)

The Bayesian methodology was used to estimate the inbreeding coefficient and outcrossing rate in diploid populations by COCKERHAM random model to allelic frequency. The proposed methodology was evaluated by data simulation. The Gibbs Sampler algorithm was implemented in the R statistical software to obtain the random samples of the inbreeding coefficient and outcrossing rate posteriors marginal distributions. The Bayesian method showed good results, because the 95 percent credible intervals contained the true parameter values to all of the selected scenes. The Gibbs Sampler convergence was checked and this validated the estimation results.(AU)