Literature DB >> 30391162

Unbiased Fitness Estimation of Pooled Barcode or Amplicon Sequencing Studies.

Fangfei Li1, Marc L Salit2, Sasha F Levy3.   

Abstract

Standard practice for phenotyping complex cell pools is to measure the fold enrichment of genotype-specific amplicons after a period of competitive growth. Here, we show that fold-enrichment measures cannot be compared across genotype pools with different fitness distributions. We develop a method to calculate an unbiased estimate of relative fitness by tracking abundances over several time points and show how to optimize experimental protocols to minimize fitness measurement error.
Copyright © 2018 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  CRISPR; Fit-Seq; amplicon sequencing; barcode sequencing; deep mutational scanning; experimental bias; fitness; fold enrichment; log-linear regression; pooled growth; reproducibility

Mesh:

Year:  2018        PMID: 30391162      PMCID: PMC6265064          DOI: 10.1016/j.cels.2018.09.004

Source DB:  PubMed          Journal:  Cell Syst        ISSN: 2405-4712            Impact factor:   10.304


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