Abstract:
:The characterization of the distribution of mutational effects is a key goal in evolutionary biology. Recently developed deep-sequencing approaches allow for accurate and simultaneous estimation of the fitness effects of hundreds of engineered mutations by monitoring their relative abundance across time points in a single bulk competition. Naturally, the achievable resolution of the estimated fitness effects depends on the specific experimental setup, the organism and type of mutations studied, and the sequencing technology utilized, among other factors. By means of analytical approximations and simulations, we provide guidelines for optimizing time-sampled deep-sequencing bulk competition experiments, focusing on the number of mutants, the sequencing depth, and the number of sampled time points. Our analytical results show that sampling more time points together with extending the duration of the experiment improves the achievable precision disproportionately compared with increasing the sequencing depth or reducing the number of competing mutants. Even if the duration of the experiment is fixed, sampling more time points and clustering these at the beginning and the end of the experiment increase experimental power and allow for efficient and precise assessment of the entire range of selection coefficients. Finally, we provide a formula for calculating the 95%-confidence interval for the measurement error estimate, which we implement as an interactive web tool. This allows for quantification of the maximum expected a priori precision of the experimental setup, as well as for a statistical threshold for determining deviations from neutrality for specific selection coefficient estimates.
journal_name
Geneticsjournal_title
Geneticsauthors
Matuszewski S,Hildebrandt ME,Ghenu AH,Jensen JD,Bank Cdoi
10.1534/genetics.116.190462subject
Has Abstractpub_date
2016-09-01 00:00:00pages
77-87issue
1eissn
0016-6731issn
1943-2631pii
genetics.116.190462journal_volume
204pub_type
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