arXiv subjects

Ernst C. Wit

Publications and source records attributed to Ernst C. Wit.

40 records · Page 3Linked to original sources

arXiv2018

De novo construction of polyploid linkage maps using discrete graphical models

Linkage maps are used to identify the location of genes responsible for traits and diseases. New sequencing techniques have created opportunities to substantially increase the density of genetic markers. Such revolutionary advances in technology have given rise to new challenges, such as creating high-density linkage maps. Current multiple testing approaches based on pairwise recombination fractions are underpowered in the high-dimensional setting and do not extend easily to polyploid species. We propose to construct linkage maps using graphical models either via a sparse Gaussian copula or a nonparanormal skeptic approach. Linkage groups (LGs), typically chromosomes, and the order of markers in each LG are determined by inferring the conditional independence relationships among large numbers of markers in the genome. Through simulations, we illustrate the utility of our map construction method and compare its performance with other available methods, both when the data are clean and contain no missing observations and when data contain genotyping errors and are incomplete. We apply the proposed method to two genotype datasets: barley and potato from diploid and polypoid populations, respectively. Our comprehensive map construction method makes full use of the dosage SNP data to reconstruct linkage map for any bi-parental diploid and polyploid species. We have implemented the method in the R package netgwas.

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arXiv2017

A penalized inference approach to stochastic block modelling of community structure in the Italian Parliament

We analyse bill cosponsorship networks in the Italian Chamber of Deputies. In comparison with other parliaments, a distinguishing feature of the Chamber is the large number of political groups. Our analysis aims to infer the pattern of collaborations between these groups from data on bill cosponsorships. We propose an extension of stochastic block models for edge-valued graphs and derive measures of group productivity and of collaboration between political parties. As the model proposed encloses a large number of parameters, we pursue a penalized likelihood approach that enables us to infer a sparse reduced graph displaying collaborations between political parties.

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arXiv2016

NEAT: an efficient network enrichment analysis test

Network enrichment analysis is a powerful method, which allows to integrate gene enrichment analysis with the information on relationships between genes that is provided by gene networks. Existing tests for network enrichment analysis deal only with undirected networks, they can be computationally slow and are based on normality assumptions. We propose NEAT, a test for network enrichment analysis. The test is based on the hypergeometric distribution, which naturally arises as the null distribution in this context. NEAT can be applied not only to undirected, but to directed and partially directed networks as well. Our simulations indicate that NEAT is considerably faster than alternative resampling-based methods, and that its capacity to detect enrichments is at least as good as the one of alternative tests. We discuss applications of NEAT to network analyses in yeast by testing for enrichment of the Environmental Stress Response target gene set with GO Slim and KEGG functional gene sets, and also by testing for associations between GO Slim categories themselves. NEAT is a flexible and efficient test for network enrichment analysis that aims to overcome some limitations of existing resampling-based tests. The method is implemented in the R package neat, which can be freely downloaded from CRAN (http://cran.r-project.org/package=neat).

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arXiv2015

Bayesian Gaussian Copula Graphical Modeling for Dupuytren Disease

Dupuytren disease is a fibroproliferative disorder with unknown etiology that often progresses and eventually can cause permanent contractures of the affected fingers. In this paper, we provide a computationally efficient Bayesian framework to discover potential risk factors and investigate which fingers are jointly affected. Our Bayesian approach is based on Gaussian copula graphical models, which are one potential way to discover the underlying conditional independence structure of variables in multivariate mixed data. In particular, we combine the semiparametric Gaussian copula with extended rank likelihood which is appropriate to analyse multivariate mixed data with arbitrary marginal distributions. For the graph structure learning, we construct a computationally efficient search algorithm which is a trans-dimensional MCMC algorithm based on a birth-death process. In addition, to make our statistical method easily accessible to other researchers, we have implemented our method in C++ and interfaced with R software as an R package BDgraph which is available online.

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