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      A Gaussian process model and Bayesian variable selection for mapping function-valued quantitative traits with incomplete phenotypic data

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      1 , 2 , 3
      Bioinformatics
      Oxford University Press

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          Abstract

          Motivation

          Recent advances in high dimensional phenotyping bring time as an extra dimension into the phenotypes. This promotes the quantitative trait locus (QTL) studies of function-valued traits such as those related to growth and development. Existing approaches for analyzing functional traits utilize either parametric methods or semi-parametric approaches based on splines and wavelets. However, very limited choices of software tools are currently available for practical implementation of functional QTL mapping and variable selection.

          Results

          We propose a Bayesian Gaussian process (GP) approach for functional QTL mapping. We use GPs to model the continuously varying coefficients which describe how the effects of molecular markers on the quantitative trait are changing over time. We use an efficient gradient based algorithm to estimate the tuning parameters of GPs. Notably, the GP approach is directly applicable to the incomplete datasets having even larger than 50% missing data rate (among phenotypes). We further develop a stepwise algorithm to search through the model space in terms of genetic variants, and use a minimal increase of Bayesian posterior probability as a stopping rule to focus on only a small set of putative QTL. We also discuss the connection between GP and penalized B-splines and wavelets. On two simulated and three real datasets, our GP approach demonstrates great flexibility for modeling different types of phenotypic trajectories with low computational cost. The proposed model selection approach finds the most likely QTL reliably in tested datasets.

          Availability and implementation

          Software and simulated data are available as a MATLAB package ‘GPQTLmapping’, and they can be downloaded from GitHub ( https://github.com/jpvanhat/GPQTLmapping). Real datasets used in case studies are publicly available at QTL Archive.

          Supplementary information

          Supplementary data are available at Bioinformatics online.

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          Most cited references41

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          Stability selection

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            A simple regression method for mapping quantitative trait loci in line crosses using flanking markers.

            The use of flanking marker methods has proved to be a powerful tool for the mapping of quantitative trait loci (QTL) in the segregating generations derived from crosses between inbred lines. Methods to analyse these data, based on maximum-likelihood, have been developed and provide good estimates of QTL effects in some situations. Maximum-likelihood methods are, however, relatively complex and can be computationally slow. In this paper we develop methods for mapping QTL based on multiple regression which can be applied using any general statistical package. We use the example of mapping in an F(2) population and show that these regression methods produce very similar results to those obtained using maximum likelihood. The relative simplicity of the regression methods means that models with more than a single QTL can be explored and we give examples of two lined loci and of two interacting loci. Other models, for example with more than two QTL, with environmental fixed effects, with between family variance or for threshold traits, could be fitted in a similar way. The ease, speed of application and generality of regression methods for flanking marker analysis, and the good estimates they obtain, suggest that they should provide the method of choice for the analysis of QTL mapping data from inbred line crosses.
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              Penalising Model Component Complexity: A Principled, Practical Approach to Constructing Priors

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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                01 October 2019
                08 March 2019
                08 March 2019
                : 35
                : 19
                : 3684-3692
                Affiliations
                [1 ] Department of Mathematics and Statistics and Organismal and Evolutionary Biology Research Programme, University of Helsinki , Helsinki, Finland
                [2 ] CSIRO Agriculture & Food , GPO Box 1600, Canberra, ACT 2601, Australia
                [3 ] Department of Mathematical Sciences, Biocenter Oulu and Infotech Oulu University of Oulu , Oulu FI-90014, Finland
                Author notes
                To whom correspondence should be addressed. E-mail: jarno.vanhatalo@ 123456helsinki.fi or zitong.li@ 123456csiro.au
                Author information
                http://orcid.org/0000-0002-6831-0211
                http://orcid.org/0000-0001-8469-7295
                http://orcid.org/0000-0003-2808-2768
                Article
                btz164
                10.1093/bioinformatics/btz164
                6761969
                30850830
                55a2897c-4f0f-43cf-b8dd-8782078f92c5
                © The Author(s) 2019. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 15 June 2018
                : 05 December 2018
                : 06 March 2019
                Page count
                Pages: 9
                Funding
                Funded by: Academy of Finland 10.13039/501100002341
                Award ID: 317255
                Categories
                Original Papers
                Genetics and Population Analysis

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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