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Nat Methods. 2007 Jan;4(1):87-93. Epub 2006 Nov 12.

SCALEs: multiscale analysis of library enrichment.

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  • 1Department of Chemical and Biological Engineering, University of Colorado, ECCH 111, Campus Box 424, Boulder, Colorado 80309, USA.


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.

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