SCALEs: multiscale analysis of library enrichment.

TitleSCALEs: multiscale analysis of library enrichment.
Publication TypeJournal Article
Year of Publication2007
AuthorsLynch, MD, Warnecke, T, and Gill, RT
JournalNature Methods
Volume4
Issue1
Start Page87
Pagination87 - 93
Date Published01/2007
Abstract

We report a genome-wide, multiscale approach to simultaneously measure the effect that the increased copy of each gene and/or operon has on a desired trait or phenotype. The method involves (i) growth selections on a mixture of several different plasmid-based genomic libraries of defined insert sizes or SCALEs, (ii) microarray studies of enriched plasmid DNA, and a (iii) mathematical multiscale analysis that precisely identifies the relevant genetic elements. This approach allows for identification of all single open reading frames and larger multigene fragments within a genomic library that alter the expression of a given phenotype. We have demonstrated this method in Escherichia coli by monitoring, in parallel, a population of >10(6) genomic library clones of different insert sizes, throughout continuous selections over a period of 100 generations.

DOI10.1038/nmeth946
Short TitleNature Methods