Identifying All Gene Products Requires Multiple Genome-Scale Measurements at Once

Researchers at the University of California, San Diego (UCSD) have discovered that multiple simultaneous genome-scale measurements are needed to identify all gene products and to determine their cellular locations and interactions with the genome. The bioengineers applied their approach to the E. coli genome to generate a detailed description of its transcription unit architecture.

In a recent Nature Biotechnology paper titled "The transcription unit architecture of the Escherichia coli genome," the researchers describe a four-step systems approach that integrates multiple genome-scale measurements on the basis of genetic information flow to identify the organizational elements and map them onto the genome sequence. 

Until now scientists have been trying to identify the genomic location of all gene products involved in complex biological processes in a single organism, but they have only been able to identify a fraction of those locations. This new discovery will allow scientists to perform full delineation of the location and use of genomic elements, according to the UCSD team.

"What's important about this paper is it now enables us to experimentally annotate genomes," says Bernard Palsson, Ph.D., a UCSD bioengineering professor and co-author of the paper. "All this information gives us a fine resolution of the contents of a genome and location of its elements.”  

The scientists used genome-scale computational models that were developed at UCSD under the systems biology program, which enabled them to compute organism designs with higher resolution and better accuracy. Currently, Dr. Palsson says that there is extensive trial and error in gene-sequencing procedures. He hopes that this metastucture of a genome that the team has developed will eliminate the trial and error and will enable them to reach new metabolic designs faster with lower failure rates.  

There are many significant implications of this new finding, he continues, such as enhancing metabolic engineering including the engineering of microorganisms to make fuels and commodity chemicals.  

"So far, scientists have been able to make chemicals to kill pathogenic strains, but we haven't been as successful as we have wanted to be," says Byung-Kwan Cho, a project scientist in the UCSD bioengineering department and the lead author of the Nature Biotechnology paper. "By using this newly discovered information, we may be able to design better drugs or medicines to kill pathogenic strains."