RT Journal Article SR Electronic T1 Measuring genetic differentiation from Pool-seq data JF bioRxiv FD Cold Spring Harbor Laboratory SP 282400 DO 10.1101/282400 A1 Valentin Hivert A1 Raphël Leblois A1 Eric J. Petit A1 Mathieu Gautier A1 Renaud Vitalis YR 2018 UL http://biorxiv.org/content/early/2018/07/12/282400.abstract AB The advent of high throughput sequencing and genotyping technologies enables the comparison of patterns of polymorphisms at a very large number of markers. While the characterization of genetic structure from individual sequencing data remains expensive for many non-model species, it has been shown that sequencing pools of individual DNAs (Pool-seq) represents an attractive and cost-effective alternative. However, analyzing sequence read counts from a DNA pool instead of individual genotypes raises statistical challenges in deriving correct estimates of genetic differentiation. In this article, we provide a method-of-moments estimator of FST for Pool-seq data, based on an analysis-of-variance framework. We show, by means of simulations, that this new estimator is unbiased, and outperforms previously proposed estimators. We evaluate the robustness of our estimator to model misspecification, such as sequencing errors and uneven contributions of individual DNAs to the pools. Finally, by reanalyzing published Pool-seq data of different ecotypes of the prickly sculpin Cottus asper, we show how the use of an unbiased FST estimator may question the interpretation of population structure inferred from previous analyses.