nQuire: a statistical framework for ploidy estimation using next generation sequencing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Clemens L. Weiß, Marina Pais, Liliana M. Cano, Sophien Kamoun, Hernán A. Burbano

ABSTRACT

BACKGROUND: Intraspecific variation in ploidy occurs in a wide range of species including pathogenic and nonpathogenic eukaryotes such as yeasts and oomycetes. Ploidy can be inferred indirectly - without measuring DNA content - from experiments using next-generation sequencing (NGS). We present nQuire, a statistical framework that distinguishes between diploids, triploids and tetraploids using NGS. The command-line tool models the distribution of base frequencies at variable sites using a Gaussian Mixture Model, and uses maximum likelihood to select the most plausible ploidy model. nQuire handles large genomes at high coverage efficiently and uses standard input file formats. RESULTS: We demonstrate the utility of nQuire analyzing individual samples of the pathogenic oomycete Phytophthora infestans and the Baker's yeast Saccharomyces cerevisiae. Using these organisms we show the dependence between reliability of the ploidy assignment and sequencing depth. Additionally, we employ normalized maximized log- likelihoods generated by nQuire to ascertain ploidy level in a population of samples with ploidy heterogeneity. Using these normalized values we cluster samples in three dimensions using multivariate Gaussian mixtures. The cluster assignments retrieved from a S. cerevisiae population recovered the true ploidy level in over 96% of samples. Finally, we show that nQuire can be used regionally to identify chromosomal aneuploidies. CONCLUSIONS: nQuire provides a statistical framework to study organisms with intraspecific variation in ploidy. nQuire is likely to be useful in epidemiological studies of pathogens, artificial selection experiments, and for historical or ancient samples where intact nuclei are not preserved. It is implemented as a stand-alone Linux command line tool in the C programming language and is available at https://github.com/clwgg/nQuire under the MIT license. More... »

PAGES

122

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12859-018-2128-z

DOI

http://dx.doi.org/10.1186/s12859-018-2128-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103128510

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29618319


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