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Peta-flogging HIV
December 2009
by Jeffrey Bouley  |  Email the author


LOS ALAMOS, N.M.—The biggest worry on the mind of the human immunodeficiency virus—well, if it had a mind, anyway—these days might not be the latest antiretroviral therapies, but rather a member of the periodic table of the elements going by the name of silicon. And that's because a cutting-edge, petascale supercomputer called Roadrunner, developed by IBM in partnership with the Los Alamos National Laboratory and the National Nuclear Security Administration, is being put to work analyzing vast quantities of genetic sequences from HIV-infected people in the hope of zeroing in on possible vaccine target areas.
The vaccine research is part of Los Alamos National Laboratory's role in the international Center for HIV/AIDS Vaccine Immunology (CHAVI) consortium, and involves studying the evolutionary history of more than 10,000 sequences from more than 400 HIV-infected individuals. To do this, two Los Alamos researchers—physicist Tanmoy Bhattacharya and HIV researcher Bette Korber—are using samples taken by CHAVI across the globe, from both chronic and acute HIV patients, to create an evolutionary genetic family tree, known as a phylogenetic tree. This will allow researchers to look for similarities in the acute versus chronic sequences that may identify areas where vaccines would be most effective.  
According to Korber, once they can identify common features of the transmitted virus, that will be a breakthrough in attempts to create a vaccine that enables recognition the original transmitted virus before the body's immune response causes the virus to react and mutate.  
But none of this would be possible, they note, without the processing power of the IBM-designed Roadrunner at Los Alamos, which on May 26, 2008, exceeded a sustained speed of 1 quadrillion (1015) calculations per second, breaking the so-called petaflop barrier. Shortly after that achievement, Roadrunner was named the world's fastest supercomputer by the TOP500 organization at the June 2008 International Supercomputing Conference in Dresden, Germany.
"The petascale supercomputer gives us the capacity to look for similarities across whole populations of acute patients," Bhattacharya explains. "At this scale, we can begin to figure out the relationships between chronic and acute infections using statistics to determine the interconnecting branches—and it is these interconnections where a specially-designed vaccine might be most effective."
"DNA sequencing technology [is] currently being revolutionized, and we are at the cusp of being able to obtain more than 100,000 viral sequences from a single person," adds Korber. "For this new kind data to be useful, computational advances will have to keep pace with the experimental, and the current study begins to move us into this new era." 
That IBM is playing a key role in this work is not as surprising at it might first seem, given the computing giant's increasingly active role in life sciences research. As reported in the November 2009 issue of ddn, IBM is making waves with its concept of the DNA Transistor, a device very much like a typical silicon microprocessor-style chip, with a 3-nanometer-diameter hole through which a DNA molecule would be passed in order to read it step-by-step quickly, possibly offering a means to achieve the elusive genetic sequencing goal that everyone calls the "$1,000 genome."
IBM is involved with a variety of other life sciences projects as well—both internally and in partnerships and collaborations with other organizations—such as bioinformatics and pattern discovery in the area of molecular biology, nanoscale dewetting transition in protein folding and research into quantum computing.
"Some years ago, we said that science was making the transition from the century of physics to the century of life sciences," says Dave Turek, vice president of supercomputing at IBM. "Because of that realization, IBM formed a computational biology center at its T.J. Watson Research Center that, among other things, uses supercomputing, the development of algorithms and the use of in silico modeling to solve a plethora of issues, including challenges in drug discovery and development."
Using in silico tools in pharmaceutical research offers obvious benefits in terms of doing more accurate modeling of efficacy and safety before actually having to spend money on animal or human studies, as well as the ability to potentially model large populations without having to use actual people. But more than that, computers can potentially model pathogens, biological processes and therapeutic agents at time scales that are very tiny and virtually impossible for humans to deal with otherwise.
"We humans operate at clock time—what we see on that wall clock or our watches," Turek says. "But biological processes can take place at time scales much smaller than that—atomic scales, and you cannot see that in a typical lab setting."  
To get down to that level of detail and truly examine important issue like protein folding, he says—or even to adequately model populations or pathogen mutations over long spans of time such as decades or centuries—requires a petascale supercomputer.
"The implications of this, now that we have that kind of computing capability, are immense," Turek notes, particularly with regard to something like vaccine development, whether for HIV or for influenza. "In the 1918 influenza pandemic, it was lethal, but it tended to stay concentrated in communities. In the modern age, with people able to travel so far and so fast, we don't have the luxury of a virus staying contained for a long time while we figure out after the fact what kind of vaccine we need. A lethal enough flu could kill millions by the time we had a vaccine.  
"Modeling likely mutations over a long period of time, using a computer-like Roadrunner," he continues, "could enable us to predict likely strains and their evolutionary steps, and be ready with enough knowledge to develop vaccines as the viruses emerge, or perhaps even before they do."  
On the HIV/AIDS front at Los Alamos, with Roadrunner to aid them, Korber and her team currently are designing three vaccines to target HIV. Their vaccine model is based on a mixture of synthetic proteins that address the virus' evasive nature—its ability to avoid triggering an immune response; its ability to mutate quickly, thereby increasing its drug resistance; its defensive cloak of sugar molecules that prevents antibodies from blocking the HIV proteins used to invade the cell; and more. Animal tests are underway, reportedly with promising results thus far and human trials expected to begin soon.

Greater than the sum
By Jeffrey Bouley  
ARMONK, N.Y.—What makes the Roadrunner petascale supercomputer at Los Alamos National Laboratory in New Mexico isn't just that it can do such an extraordinary number of calculations so quickly. It's also the fact this computer was built in a very novel manner.  
IBM didn't simply aim to build a bigger supercomputer, notes Dave Turek, vice president of supercomputing at IBM. Instead, it built a hybrid system, which gets its processing power from 12,240 IBM PowerXCell 8i Cell Broadband Engine processors that are derived from the same microchips that power today's most popular videogame consoles. In addition, 6,562 AMD Opteron Dual-Core processors perform basic computer functions, freeing the IBM PowerXCell 8i chips for the math-intensive calculations that are their specialty.  
This hybrid architecture, which optimizes the strength of multiple types of processors, is analogous to that of a hybrid car, and offering similar benefits in terms of not only efficiency, but also energy usage. If Roadrunner had been built with standard x86 chips alone, the system reportedly would have been significantly larger and would have required much more power.  
"The power problem is one that affects our industry ubiquitously," Turek notes. "Hybridization allows us to pick and choose and manage the power profile of the system to get an extremely high level of performance per watt. If we had tried to build Roadrunner without a hybrid approach, we would have blown both the space allocation and the power budget at Los Alamos by far."

Roadrunner races to its next duty  
By Jeffrey Bouley  
LOS ALAMOS, N.M.—The work on HIV vaccine research isn't the only thing the Roadrunner supercomputer has been up to. During the same six-month period that it was doing that, which ended in September, Los Alamos researchers had Roadrunner, working on 10 unclassified projects. Some of the other projects besides HIV include understanding the nature of dark matter and dark energy, understanding the non-linear physics of high-power lasers, examining how shockwaves cause materials to fail, and unraveling how and why some stars explode.  
But in the end, while Roadrunner has advanced science in a number of areas, all of these projects were run on the supercomputer as a kind of  "shakedown" process so that scientists could optimize the way large codes are able to run on the machine and ensure that it could handle huge workloads.
Now Roadrunner is in the process of transition to classified computing for its intended mission: to assure the safety, security, and reliability of the U.S. nuclear deterrent.

Code: E120904



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