Over the last 20 years, the sequencing of the human genome, along with
related organisms, has represented one of the largest scientific
endeavors in the history of humankind. The information collected from
genome sequencing will provide the raw data for the field of
bioinformatics, where computer science and biology meet.
Since the publication of the first full genome sequence in the
mid-1990s, scientists have been working to identify the genomic
location of all the gene products involved in the complex biological
processes in a single organism. However, they have only been able to
identify a fraction of those locations. Until now.
Bioengineers at UC San Diego have made a breakthrough development
that will now allow scientists to perform full delineation of the
location and use of genomic elements. The researchers 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.
In a recent Nature Biotechnology paper, 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. The bioengineers have applied this approach to the E. coli genome to generate a detailed description of its transcrip¬tion unit architecture.
"What’s important about this paper is it now enables us to
experimentally annotate genomes," said Bernard Palsson, 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. This is a fine blueprint of a genetic makeup
of the genome. We have been able to use genome scale computational
models that have been developed at UCSD under the systems biology
program, which have enabled us to compute organism designs with higher
resolution or better accuracy, which has not been possible before. It
takes a lot of the guesswork out of making an organism. Currently there
is extensive trial and error in gene sequencing procedures. Hopefully
this ‘metastucture’ of a genome that we have developed will eliminate
that trial and error and will enable us to reach new metabolic designs
faster with lower failure rates."
Palsson said there are many significant implications of this new
finding, such as enhancing metabolic engineering (such as the
engineering of microorganisms to make fuels and commodity chemicals).
The UCSD bionengineers combined several computation methods with
information mapping in this research. "There are several high
throughput methods developed recently like deep sequencing and micro
array systems that we used," said Byung-Kwan Cho, a project scientist
in the UCSD bioengineering department and the lead author of the Nature
Biotechnology paper. "We wanted to integrate all the information into
one format to describe the genome. We have genome sequences but we
don’t know what all of them are. When we sequenced the Human Genome we
thought we knew everything but actually we don’t know everything. There
are lots of data generation techniques and a huge amount of data
available. So we were able to map all of this information into one
"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," Cho added. "By using this newly discovered information we may
be able to design better drugs or medicines to kill pathogenic strains.
That’s the important point of this research — there is a huge amount
of applications for this. The E. coli bacteria is just the beginning."
Source : University of California – San Diego