Biologist John Tyson, who studies the cell cycle, is a leader in applying mathematical models in molecular cell biology. However, comparing the results of a mathematical model to experimental data is difficult because mathematical results are quantitative (numbers) while much experimental data is qualitative (trends). The mathematical biologist must figure out how to set the numerical values of the â€˜parametersâ€™ in the model equations in order to create an accurate representation of what is going on inside the cell. A simple example is the conversion between Fahrenheit and Celsius temperatures, said mathematician Layne Watson. "You could use several pairs of Fahrenheit and Celsius readings for the same temperature, and try to deduce the formula for converting between the temperature scales."
Previously, Tyson worked with simpler models whose parameters could be determined by trial and error, a process modelers call "parameter twiddling." But he and his coworker, Kathy Chen, wanted to characterize all the protein interactions regulating the cell cycle of budding yeast (the yeast cells familiar to bakers and brewers, and a favorite organism of molecular biologists, as well). "Such fundamental research on the cell cycle of budding yeast provides a basis for understanding the reproduction of human cells and is relevant to the causes and treatment of cancer, to tissue regeneration, and to the control of many pathogens," Tyson said.
For the budding yeast cell cycle, the experimental data consists of observed traits of 130 mutant yeast strains constructed by disabling and/or over-expressing the genes that encode the proteins of the regulatory network. The model has 143 parameters that need to be estimated from the data. "That is a big problem," said Watson. "You can't do that by hand. You can't even do it on a laptop. It takes a supercomputer."
In fact, it required more than 20,000 CPU hours on System X, a 2200 processor parallel computer, using two new algorithms, DIRECT (DIviding RECTangles) and MADS (Mesh Adaptive Direct Search), to estimate the 143 parameters.
"With a tool like this scientists can spend more time working on the model and less time twiddling parameters," said Tyson.
The research is due to appear in 2007 in the Journal of Global Optimization, in the article "Deterministic Parallel Global Parameter Estimation for a Model of the Budding Yeast Cell Cycle," by Thomas D. Panning, Layne T. Watson, Nicholas A. Allen, Katherine C. Chen, Clifford A. Shaffer, and John J. Tyson.
Panning, who is from Tulsa, Okla., received his master of science in computer science in May 2006 and is currently working as a programmer in Germantown, Md. Watson, of Blacksburg, is professor of computer science in the College of Engineering and professor of mathematics in the College of Science. Allen, who is from Columbia, Md., received his Ph.D. in computer science in November 2005 and is now with Microsoft. Chen, of Blacksburg, is a research scientist biological sciences in the College of Science. Shaffer, of Newport, is associate professor of computer science. Tyson, of Blacksburg, is a University Distinguished Professor of biological sciences.
The Virginia Tech computer science team created massively parallel versions of a deterministic global search algorithm, DIRECT, and a deterministic local search algorithm, MADS, to do the twiddling, and then combined the results. "A deterministic global search algorithm systematically explores the parameter space, finding good values," Watson said. "Then the local search algorithm improves the values from the starting points found by the global algorithm."
The parallel computer programs can now be used by others for similar problems. "The parameters found for the budding yeast cell cycle model are good until the next scientist invalidates them with new experimental data. That could be years from now or next week. That's the way science works," says Watson.
Susan Trulove | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction