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Biology subjects

Aguilar, I.

Publications and source records attributed to Aguilar, I..

4 recordsLinked to original sources

Learning genetic values of individuals with incomplete pedigree, genomic and phenotypic data

Prediction of outcomes is important in personalized medicine, animal and plant breeding. Typical inputs for building prediction models in agriculture include genealogies, molecular markers and phenotypes. Information is seldom complete, i.e., there may be individuals that lack at least one of such inputs. For instance, all individuals may possess pedigree data but only a fraction is genotyped for molecular markers. A solution for such situation is known as "single-step best linear unbiased prediction" (SS-BLUP). A more general scenario is one where, in addition to the setting of SS-BLUP, there are subjects with genomic data but lacking genealogy, with or without phenotypes. Our study presents a novel "single-step" prediction method that accommodates a wider degree of incompleteness than SS-BLUP. It does not employ imputation or approximations and is based on basic Bayesian principles of combining distinct prior opinions. The proposed method, Hy-BLUP ("Hy" for "hybrid") uses a prior that combines knowledge from the population about variation derived from pedigree and from markers, as if these two sources of information were independent. Such assumption may over-state prior precision, but Bayesian theory dictates that it should be over-ridden as information from data accrues.The Bayesian logic defines the weights assigned to the sources implictly. However, additional weights (wAand wG for pedigree and genomic information, respectively) may be introduced as tuning parameters. From an inferential perspective, the weights and the variance components are not jointly identified in the likelihood function. However, given the variance components, some Bayesian learning about the weights can be obtained. The prior induces a precision matrix (inverse of the covariance matrix) automatically, without use of cumbersome matrix algebra arguments or approximations. The prior is combined with the data and, given the weights (if any) and variance parameters, the estimating "mixed model" equations can be built and computed directly. The method was evaluated using a publicly available data set consisting of 599 inbred lines of wheat genotyped for binary markers and with full pedigree information; the target trait was grain yield. The evaluation used several experiments that simulated various patterns of incompleteness and a training-testing layout supplemented by bootstrapping or random reconstruction of sets. There were minor differences between SS-BLUP and Hy-BLUP in predictive ability.The discussion includes a multiple-trait generalization of Hy-BLUP that may be useful in situations where some individuals are not phenotyped for some trait (e.g., animal carcass weight in a fully-pedigreed breeding nucleus) while others (not pedigreed) are genotyped, scored and destroyed for commercial or laboratory purposes. The study provides a proof-of-concept of the potential usefulness of Hy-BLUP for routine genome-enabled prediction in individuals with irregular patterns of information.

genetics↗

Lateral Orbitofrontal Cortex Encodes Presence of Risk and Subjective Risk Preference During Decision-Making

Adaptive decision-making requires consideration of objective risks and rewards associated with each option, as well as subjective preference for risky/safe alternatives. Inaccurate risk/reward estimations can engender excessive risk-taking, a central trait in many psychiatric disorders. The lateral orbitofrontal cortex (lOFC) has been linked to many disorders associated with excessively risky behavior and is ideally situated to mediate risky decision-making. Here, we used single-unit electrophysiology to measure neuronal activity from lOFC of freely moving rats performing in a punishment-based risky decision-making task. Subjects chose between a small, safe reward and a large reward associated with either 0% or 50% risk of concurrent punishment. lOFC activity repeatedly encoded current risk in the environment throughout the decision-making sequence, signaling risk before, during, and after a choice. In addition, lOFC encoded reward magnitude, although this information was only evident during action selection. A Random Forest classifier successfully used neural data accurately to predict the risk of punishment in any given trial, and the ability to predict choice via lOFC activity differentiated between and risk-preferring and risk-averse rats. Finally, risk preferring subjects demonstrated reduced lOFC encoding of risk and increased encoding of reward magnitude. These findings suggest lOFC may serve as a central decision-making hub in which external, environmental information converges with internal, subjective information to guide decision-making in the face of punishment risk.

neuroscience↗

Single-step genome-wide association study for susceptibility to Teratosphaeria nubilosa and precocity of vegetative phase change in Eucalyptus globulus

Mycosphaerella leaf disease (MLD) is one of the most prevalent foliar diseases of E. globulus plantations around the world. Since resistance management strategies have not been effective in commercial plantations, breeding to develop more resistant genotypes is the most promising strategy. Available genomic information can be used to detect genomic regions associated with resistance to MLD, which could significantly speed up the process of genetic improvement. In this study, we investigated the genetic basis of MLD resistance in a breeding population of E. globulus which was genotyped with the EUChip60K SNP array. Resistance to MLD was evaluated for resistance of the juvenile foliage, as defoliation and leaf spot severity, and for precocity of change to resistant adult foliage. Genome-wide association studies (GWAS) were carried out applying four Single-SNP models, a Genomic Best Linear Unbiased Prediction (GBLUP-GWAS) approach, and a Single-step genome-wide association study (ssGWAS). The Single-SNP and GBLUP-GWAS models detected 13 and 16 SNP-trait associations in chromosomes 2, 3 y 11; whereas the ssGWAS detected 66 SNP-trait associations in the same chromosomes, and additional significant SNP-trait associations in chromosomes 5 to 9 for the precocity of phase change (proportion of adult foliage). For this trait, the two main regions in chromosomes 3 and 11 were identified for the three approaches. The SNPs identified in these regions were positioned near the key miRNA genes, miR156.5 and miR157.4, which have a main role in the regulation of the timing of vegetative change, and also in the response to environmental stresses in plants. Our results outlined that ssG-WAS was more powerful in detecting regions that affect resistance than conventional GWAS approaches. Additionally, suggest a polygenic genetic architecture for the heteroblastic transition in E. globulus and identified useful SNP markers for the development of marker-assisted selection strategies for resistance.

plant biology↗

Exact p-values for large-scale single step genome-wide association, with an application for birth weight in American Angus

BACKGROUNDSingle Step GBLUP (SSGBLUP) is the most comprehensive method for genomic prediction. Point estimates of marker effects from SSGBLUP are often used for Genome Wide Association Studies (GWAS) without a formal framework of hypothesis testing. Our objective was to implement p-values for GWAS studies in the ssGBLUP framework, showing algorithms, computational procedures, and an application to a large beef cattle population. METHODSP-values were obtained based on the prediction error (co)variance for SNP, which uses the inverse of the coefficient matrix and formulas to compute SNP effects. RESULTSComputation of p-values took a negligible time for a dataset with almost 2 million animals in the pedigree and 1424 genotyped sires, and no inflation was observed. The SNP passing the Bonferroni threshold of 5.9 in the -log10 scale were the same as those that explained the highest proportion of additive genetic variance, but the latter was penalized (as GWAS signal) by low allele frequency. CONCLUSIONThe exact p-value for SSGWAS is a very general and efficient strategy for QTL detection and testing. It can be used in complex data sets such as used in animal breeding, where only a proportion of pedigreed animals are genotyped.

genomics↗