Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. A Statistical Guide to the Design of Deep Mutational Scanning Experiments
 
research article

A Statistical Guide to the Design of Deep Mutational Scanning Experiments

Matuszewski, Sebastian  
•
Hildebrandt, Marcel E.
•
Ghenu, Ana-Hermina
Show more
2016
Genetics

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.

  • Details
  • Metrics
Type
research article
DOI
10.1534/genetics.116.190462
Web of Science ID

WOS:000383998500009

Author(s)
Matuszewski, Sebastian  
Hildebrandt, Marcel E.
Ghenu, Ana-Hermina
Jensen, Jeffrey D.  
Bank, Claudia  
Date Issued

2016

Publisher

Genetics Society America

Published in
Genetics
Volume

204

Issue

1

Start page

77

End page

87

Subjects

experimental design

•

experimental evolution

•

distribution of fitness effects

•

mutation

•

population genetics

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPJENSEN  
Available on Infoscience
November 21, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/131487
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés