R.J. Nichols et al., “Phenotypic landscape of a bacterial cell,” Cell, 144:143-56, 2011. Free F1000 Evaluation
Advances in sequencing technology have inundated scientists with genomics data but left them with a drought of corresponding phenotypes. To address this problem, first author Robert Nichols of the University of California, San Francisco, and his colleagues built a database of E. coli phenotypes and demonstrated how this database can be used to identify the functions of orphan genes—known genes without an assigned function.
The researchers grew almost 4,000 bacterial mutants under 324 stress conditions, including antibiotics and other environmental stresses such as temperature and pH extremes, and quantified the growth phenotypes based on the resulting colony size. They tried to “mimic as many different stresses as we could think of and realistically screen,” said Nichols, to create a comprehensive database of the relationships between genes, environment, and growth—a first step to determining phenotype.
The researchers found a group of orphan genes that changed growth patterns in a number of environments. Surprisingly, despite their observed importance, these genes were not well conserved beyond this class of bacteria, suggesting that “gene conservation is not necessarily well correlated with ‘importance,’” wrote F1000 Member Stephen Spiro in his evaluation.
The sum of all this work is E. coli Wiki, a publicly accessible database to help researchers identify potential genes and pathways associated with their observed phenotypes. “It’s a guidepost toward the function of an unknown gene,” said F1000 Member Larry Mulcahy. The database is available at: http://ecoliwiki.net/tools/chemgen/