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Detecting epistasis from an ensemble of adapting populations.

ABSTRACT: The role that epistasis plays during adaptation remains an outstanding problem, which has received considerable attention in recent years. Most of the recent empirical studies are based on ensembles of replicate populations that adapt in a fixed, laboratory controlled condition. Researchers often seek to infer the presence and form of epistasis in the fitness landscape from the time evolution of various statistics averaged across the ensemble of populations. Here, we provide a rigorous analysis of what quantities, drawn from time series of such ensembles, can be used to infer epistasis for populations evolving under weak mutation on finite-site fitness landscapes. First, we analyze the mean fitness trajectory-that is, the time course of the ensemble average fitness. We show that for any epistatic fitness landscape and starting genotype, there always exists a non-epistatic fitness landscape that produces the exact same mean fitness trajectory. Thus, the presence of epistasis is not identifiable from the mean fitness trajectory. By contrast, we show that two other ensemble statistics-the time evolution of the fitness variance across populations, and the time evolution of the mean number of substitutions-can detect certain forms of epistasis in the underlying fitness landscape.

SUBMITTER: McCandlish DM

PROVIDER: S-EPMC5656054 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Detecting epistasis from an ensemble of adapting populations.

McCandlish David M DM Otwinowski Jakub J Plotkin Joshua B JB

Evolution; international journal of organic evolution 20150820 9

The role that epistasis plays during adaptation remains an outstanding problem, which has received considerable attention in recent years. Most of the recent empirical studies are based on ensembles of replicate populations that adapt in a fixed, laboratory controlled condition. Researchers often seek to infer the presence and form of epistasis in the fitness landscape from the time evolution of various statistics averaged across the ensemble of populations. Here, we provide a rigorous analysis ...[more]

PMID: 26194030

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Project description:BACKGROUND: Epistasis is recognized fundamentally important for understanding the mechanism of disease-causing genetic variation. Though many novel methods for detecting epistasis have been proposed, few studies focus on their comparison. Undertaking a comprehensive comparison study is an urgent task and a pathway of the methods to real applications. RESULTS: This paper aims at a comparison study of epistasis detection methods through applying related software packages on datasets. For this purpose, we categorize methods according to their search strategies, and select five representative methods (TEAM, BOOST, SNPRuler, AntEpiSeeker and epiMODE) originating from different underlying techniques for comparison. The methods are tested on simulated datasets with different size, various epistasis models, and with/without noise. The types of noise include missing data, genotyping error and phenocopy. Performance is evaluated by detection power (three forms are introduced), robustness, sensitivity and computational complexity. CONCLUSIONS: None of selected methods is perfect in all scenarios and each has its own merits and limitations. In terms of detection power, AntEpiSeeker performs best on detecting epistasis displaying marginal effects (eME) and BOOST performs best on identifying epistasis displaying no marginal effects (eNME). In terms of robustness, AntEpiSeeker is robust to all types of noise on eME models, BOOST is robust to genotyping error and phenocopy on eNME models, and SNPRuler is robust to phenocopy on eME models and missing data on eNME models. In terms of sensitivity, AntEpiSeeker is the winner on eME models and both SNPRuler and BOOST perform well on eNME models. In terms of computational complexity, BOOST is the fastest among the methods. In terms of overall performance, AntEpiSeeker and BOOST are recommended as the efficient and effective methods. This comparison study may provide guidelines for applying the methods and further clues for epistasis detection.

Dataset Information

Detecting epistasis from an ensemble of adapting populations.

Publications

Detecting epistasis from an ensemble of adapting populations.

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