Researchers at the Institute for Genomic Biology at the University of Illinois have developed a way to harness the prodigious quantities of both genomic and metabolic data being generated with high-throughput genomics and other techniques.
They have developed an algorithm that automatically integrates both data sets. The model, called probabilistic regulation of metabolism (PROM), enables researchers to perturb a given regulatory gene or metabolic process and see how that affects the entire network.
"PROM provides a platform for studying the behavior of networks in a wide range of different conditions," says principal investigator Nathan Price, an associate professor of chemical and biomolecular engineering at Illinois.
Using this model the researchers have created the first genome-scale, regulatory-metabolic network of Mycobacterium tuberculosis. Their results were published online by PNAS on September 27.
Using E. Coli as a benchmark, Price and graduate student Sriram Chandrasekaran showed that PROM was more accurate and comprehensive than the previous model for E. Coli, which had been done by hand and published in 2004.
After using E. Coli as a proof of principle, they targeted tuberculosis, a bacterium that has not been as thoroughly studied as E. Coli. Price and Chandrasekaran had less than half the amount of data then they had for E. Coli and were still able to create a model that predicted knockout phenotypes 95 percent of the time, says Price.
Price and Chandrasekaran built the algorithm using microarray data, transcription-factor interactions that regulate metabolic reactions, and knock-out phenotypes. The method is both accurate and fast. PROM may prove particularly helpful to tuberculosis researchers because, although when tuberculosis is growing it can be killed, the real challenge is to target the bacterium during its dormant or quiescent stage. PROM may enable researchers to identify and target the pathways keeping the cells alive during dormancy.
PROM also represents a major advance because it successfully integrates the statistically derived transcriptional regulatory network with a biochemically derived metabolic network.
"That is the new part," says Price. "People have created regulatory models and metabolic models. But there has been nothing before that could combine them in this automated fashion. It is difficult to get these two to talk to each other in the right way."
Price and Chandrasekaran created an algorithm that makes use of probability. Earlier models used a Boolean or a binary approach, in which a gene is either on or off. PROM can account for a gene or enzyme that can also be part way on or part way off, so it acts more like a rheostat than a toggle switch.
"People were stuck here for a long time. That's why PROM is such a nice method. It's sort of Boolean but it's probabilistic Boolean. It does allow us to have a continuous variation," says Price.
"These models can guide genome-scale synthetic biology," he adds. "And understanding how the networks are put together lays the foundation for us to design genomes that encode for networks that behave in the way we want them to, such as engineering microbes to convert environmental toxins into biofuels, for example."
Melissa Edwards | EurekAlert!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences