TY - JOUR
T1 - A survey of methods and tools to detect recent and strong positive selection
AU - Pavlidis, Pavlos
AU - Alachiotis, Nikolaos
N1 - Funding Information:
This study was partially funded by an FP7-PEOPLE Grant [FP7-PEOPLE-2013-IEF EVOGREN (625057)] to PP.
Publisher Copyright:
© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
PY - 2017
Y1 - 2017
N2 - Positive selection occurs when an allele is favored by natural selection. The frequency of the favored allele increases in the population and due to genetic hitchhiking the neighboring linked variation diminishes, creating so-called selective sweeps. Detecting traces of positive selection in genomes is achieved by searching for signatures introduced by selective sweeps, such as regions of reduced variation, a specific shift of the site frequency spectrum, and particular LD patterns in the region. A variety of methods and tools can be used for detecting sweeps, ranging from simple implementations that compute summary statistics such as Tajima's D, to more advanced statistical approaches that use combinations of statistics, maximum likelihood, machine learning etc. In this survey, we present and discuss summary statistics and software tools, and classify them based on the selective sweep signature they detect, i.e., SFS-based vs. LD-based, as well as their capacity to analyze whole genomes or just subgenomic regions. Additionally, we summarize the results of comparisons among four open-source software releases (SweeD, SweepFinder, Sweep-Finder2, and OmegaPlus) regarding sensitivity, specificity, and execution times. In equilibrium neutral models or mild bottlenecks, both SFS- and LD-based methods are able to detect selective sweeps accurately. Methods and tools that rely on LD exhibit higher true positive rates than SFS-based ones under the model of a single sweep or recurrent hitchhiking. However, their false positive rate is elevated when a misspecified demographic model is used to represent the null hypothesis. When the correct (or similar to the correct) demographic model is used instead, the false positive rates are considerably reduced. The accuracy of detecting the true target of selection is decreased in bottleneck scenarios. In terms of execution time, LD-based methods are typically faster than SFS-based methods, due to the nature of required arithmetic.
AB - Positive selection occurs when an allele is favored by natural selection. The frequency of the favored allele increases in the population and due to genetic hitchhiking the neighboring linked variation diminishes, creating so-called selective sweeps. Detecting traces of positive selection in genomes is achieved by searching for signatures introduced by selective sweeps, such as regions of reduced variation, a specific shift of the site frequency spectrum, and particular LD patterns in the region. A variety of methods and tools can be used for detecting sweeps, ranging from simple implementations that compute summary statistics such as Tajima's D, to more advanced statistical approaches that use combinations of statistics, maximum likelihood, machine learning etc. In this survey, we present and discuss summary statistics and software tools, and classify them based on the selective sweep signature they detect, i.e., SFS-based vs. LD-based, as well as their capacity to analyze whole genomes or just subgenomic regions. Additionally, we summarize the results of comparisons among four open-source software releases (SweeD, SweepFinder, Sweep-Finder2, and OmegaPlus) regarding sensitivity, specificity, and execution times. In equilibrium neutral models or mild bottlenecks, both SFS- and LD-based methods are able to detect selective sweeps accurately. Methods and tools that rely on LD exhibit higher true positive rates than SFS-based ones under the model of a single sweep or recurrent hitchhiking. However, their false positive rate is elevated when a misspecified demographic model is used to represent the null hypothesis. When the correct (or similar to the correct) demographic model is used instead, the false positive rates are considerably reduced. The accuracy of detecting the true target of selection is decreased in bottleneck scenarios. In terms of execution time, LD-based methods are typically faster than SFS-based methods, due to the nature of required arithmetic.
KW - Positive selection
KW - Selective sweep
UR - http://www.scopus.com/inward/record.url?scp=85045151344&partnerID=8YFLogxK
U2 - 10.1186/s40709-017-0064-0
DO - 10.1186/s40709-017-0064-0
M3 - Article
AN - SCOPUS:85045151344
SN - 1790-045X
VL - 24
JO - Journal of Biological Research (Greece)
JF - Journal of Biological Research (Greece)
IS - 1
M1 - 7
ER -