(mentions HSMN-CMT ) Superlinks to identify genetic culprits

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Superlinks to identify genetic culprits

http://www.isgtw.org/?pid=1001998

A graphic map of a particularly complex family tree. The squares represent

males, while the circles represent females. Individuals affected by a genetic

mutation are represented with red squares or circles. Yellow lines indicate a

marriage between relatives. Image courtesy of Kwanghyuk (Danny) Lee, Baylor

College of Medicine.

Once scientists know which mutation causes a disease, they can apply that

knowledge in their search for a cure. Likewise, doctors can recommend lifestyle

changes that will alter the course of the disease. But the computer analysis

used to identify these mutations would take years to complete on a single

computer.

Superlink-online, a distributed system developed at the Technion-Israel

Institute of Technology, helps researchers perform their analyses in a matter of

days by distributing the computations over thousands of computers worldwide.

Geneticists submit their data through the web portal with a single click and get

their results via email, ready to use. Behind the scenes, the system splits the

computations into hundreds of thousands of independent jobs, runs them using the

available resources, and assembles the results back into a single data set.

Geneticists use Superlink-online to do statistical computations called genetic

linkage analysis. The analysis maps the genealogy and the genetic makeup of the

genealogy's members onto a graphical model that represents the likelihood of a

gene being linked to a disease. The goal is to determine the location of the

genes that provoke a disease.

Superlink ran on a single computer in 2002 when it was first released by Dan

Geiger and his students at the Technion. By 2005, as more computer power was

needed to perform increasingly complex analyses, then-doctoral student Mark

Silberstein began working on a distributed version. Silberstein and his advisor,

Assaf Schuster, realized that the only way to meet the research's demand for

increasingly powerful computing was to enable opportunistic use of non-dedicated

computers.

" [The data] was too complex to analyze on one CPU..., " said Silberstein. " It was

impossible to provide 'service' with this quality of service. " The opportunistic

model was chosen, explained Silberstein, because " with literally zero budget for

purchasing and maintaining dedicated hardware, and with the actual resource

demand reaching thousands of CPUs, we could not afford any other model. "

In early 2006, thanks to close collaboration with the Condor team at the

University of Wisconsin-Madison, the first version of Superlink-online was

released. At the time, the system used UW-Madison's Condor pool and the

Technion's own home-brewed Condor pool, which had about 100 CPUs. Eventually,

additional resources came from the Open Science Grid, EGEE, and the

Superlink@Technion community grid, which uses the idle cycles on the home

computers of volunteers.

It's a powerful combination. During a 3-month period, over 25,000 non-dedicated

hosts from the grids Superlink-online uses have been actively participating in

the computations, reaching a maximum effective throughput roughly equal to that

of a dedicated cluster of up to 8,000 cores.

With access to that much computing power, the system has enabled hundreds of

geneticists worldwide to analyze much larger data sets, producing results 100

times faster than the serial version. As a result, several rare disease-causing

mutations have been found, including the mutations that cause Hereditary Motor

and Sensory Neuropathy, " Uncomplicated " Hereditary Spastic Paraplegia, and

Ichthyosis.

What's next? Silberstein and his colleagues are finalizing a version of

Superlink-online that will significantly extend its power. In addition to the

aforementioned grids, the new system will access the Tokyo Institute of

Technology's Tsubame supercomputer.

—Marcia Teckenbrock, for iSGTW and Open Science Grid