PMID:17099705
| Citation |
Lynch, MD, Warnecke, T and Gill, RT (2007) SCALEs: multiscale analysis of library enrichment. Nat. Methods 4:87-93 |
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| 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. |
| Links |
PubMed Online version:10.1038/nmeth946 |
| Keywords |
DNA Fragmentation; DNA, Bacterial/genetics; Directed Molecular Evolution; Escherichia coli/genetics; Gene Dosage; Genomic Library; Genomics/methods; Models, Genetic; Oligonucleotide Array Sequence Analysis/methods; Open Reading Frames/genetics; Phenotype; Plasmids/genetics; Time Factors |
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