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  1. Nielsen, Rasmus (Ed.)
    Abstract

    An important goal of evolutionary genomics is to identify genomic regions whose substitution rates differ among lineages. For example, genomic regions experiencing accelerated molecular evolution in some lineages may provide insight into links between genotype and phenotype. Several comparative genomics methods have been developed to identify genomic accelerations between species, including a Bayesian method called PhyloAcc, which models shifts in substitution rate in multiple target lineages on a phylogeny. However, few methods consider the possibility of discordance between the trees of individual loci and the species tree due to incomplete lineage sorting, which might cause false positives. Here, we present PhyloAcc-GT, which extends PhyloAcc by modeling gene tree heterogeneity. Given a species tree, we adopt the multispecies coalescent model as the prior distribution of gene trees, use Markov chain Monte Carlo (MCMC) for inference, and design novel MCMC moves to sample gene trees efficiently. Through extensive simulations, we show that PhyloAcc-GT outperforms PhyloAcc and other methods in identifying target lineage-specific accelerations and detecting complex patterns of rate shifts, and is robust to specification of population size parameters. PhyloAcc-GT is usually more conservative than PhyloAcc in calling convergent rate shifts because it identifies more accelerations on ancestral than on terminal branches. We apply PhyloAcc-GT to two examples of convergent evolution: flightlessness in ratites and marine mammal adaptations, and show that PhyloAcc-GT is a robust tool to identify shifts in substitution rate associated with specific target lineages while accounting for incomplete lineage sorting.

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

    Polygenic risk score (PRS) has been widely exploited for genetic risk prediction due to its accuracy and conceptual simplicity. We introduce a unified Bayesian regression framework, NeuPred, for PRS construction, which accommodates varying genetic architectures and improves overall prediction accuracy for complex diseases by allowing for a wide class of prior choices. To take full advantage of the framework, we propose a summary-statistics-based cross-validation strategy to automatically select suitable chromosome-level priors, which demonstrates a striking variability of the prior preference of each chromosome, for the same complex disease, and further significantly improves the prediction accuracy.

    Results

    Simulation studies and real data applications with seven disease datasets from the Wellcome Trust Case Control Consortium cohort and eight groups of large-scale genome-wide association studies demonstrate that NeuPred achieves substantial and consistent improvements in terms of predictive r2 over existing methods. In addition, NeuPred has similar or advantageous computational efficiency compared with the state-of-the-art Bayesian methods.

    Availability and implementation

    The R package implementing NeuPred is available at https://github.com/shuangsong0110/NeuPred.

    Supplementary information

    Supplementary data are available at Bioinformatics online.

     
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  7. Abstract The multiple-try Metropolis method is an interesting extension of the classical Metropolis–Hastings algorithm. However, theoretical understanding about its usefulness and convergence behavior is still lacking. We here derive the exact convergence rate for the multiple-try Metropolis Independent sampler (MTM-IS) via an explicit eigen analysis. As a by-product, we prove that an naive application of the MTM-IS is less efficient than using the simpler approach of “thinned” independent Metropolis–Hastings method at the same computational cost. We further explore more variants and find it possible to design more efficient algorithms by applying MTM to part of the target distribution or creating correlated multiple trials. 
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    Free, publicly-accessible full text available August 1, 2024
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