title: SCALEs: multiscale analysis of library enrichment.
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.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, ECCH 111, Campus Box 424, Boulder, Colorado 80309, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lynch
authors.forename: Tanya
authors.initials: T
authors.lastname: Warnecke
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Gill
mesh_terms: D053938:DNA Fragmentation; D004269:DNA, Bacterial / Q000235:genetics*; D019020:Directed Molecular Evolution; D004926:Escherichia coli / Q000235:genetics*; D018628:Gene Dosage; D015698:Genomic Library; D023281:Genomics / Q000379:methods; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D013997:Time Factors
chemical_list: D004269:DNA, Bacterial