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ISB, U of Luxembourg to Sequence Families To Link Genetic, Phenotypic Data to Disease

The Institute for Systems Biology and the Center for Systems Biology Luxembourg, a new partnership between ISB and the University of Luxembourg, will collaborate to sequence the genomes of at least 100 individuals and develop methods to analyze the data as part of a disease-focused study, the government of Luxembourg said last week.
The project will study the genomes of families whose members have been diagnosed with certain diseases, along with controls, and correlate their genomic data with phenotypic and clinical data. But for the first two years, before large-scale sequencing actually begins, the researchers will explore different sequencing technologies and develop computational tools to analyze genetic variability between individuals.
“We are pretty convinced that the sequencing technologies that exist right now are not quite at a stage where you can do, at least easily, complete personal genome sequences,” ISB President Lee Hood told In Sequence this week. He and David Galas, a professor at ISB and former head of the Department of Energy’s Human Genome Project, are jointly leading the project.
That is why in the first year of the study, researchers will focus on exploring different sequencing methods. “Probably in year two [we will] decide on a technology and really start pushing it,” Hood said. “The hope, frankly, is that we get the throughput and the cost to the stage where we can be doing thousands rather than hundreds of genome sequences.”
According to Hood, current technologies suffer from high error rates, which means they require high coverage to yield a high-quality consensus sequence, which in turn makes sequencing projects expensive.
“We are really looking for solutions that have much higher quality data, and, frankly, we’d love solutions that have longer reads,” he said. “But that may or may not be possible to get on a scale that we are interested in.”
ISB currently has two Illumina Genome Analyzers in-house and is looking to acquire an Applied Biosystems SOLiD sequencer, he said. The institute is also exploring technology developed by George Church at Harvard.
He added that the institute is “not at this point” planning to acquire a Helicos sequencer, which he said has a “very high error rate,” mainly because of its “pretty staggering” cost.
Within the next six months, the scientists will probably sequence four or five complete genomes from a single family, according to Hood. The data for these will likely not be generated by ISB or its collaborators but “by one of the existing sequencing companies” in the US, he said. He declined to reveal which technology will be used.
ISB scientists will use data from these genomes as a standard to develop new computational tools to define individual variability and “uniqueness,” Hood said.
“We would like to push the whole business of sequence analysis to the next stage beyond just the SNP analyses that 23andMe and Navigenics are doing,” he said, referring to direct-to-consumer DNA analysis shops. “It’s more along the lines of the 1,000 Genomes [Project], although we are going to be doing families rather than individuals.”
The project will not only be focused on genomic data. For each of the sequenced samples, the researchers also plan to generate molecular phenotypic data, such as blood protein fingerprints, and other phenotypic data, and relate these factors to clinical data.
“It’s a broad, very comprehensive project that is multidimensional and will integrate many different types of data,” Hood said.
This will in part be made possible by the Integrated BioBank of Luxembourg, a new biological sample repository being built by researchers in Luxembourg in collaboration with the Translational Genomics Research Institute in Arizona. This biobank, Hood said, will “make it possible for us to collect enormous clinical data longitudinally on these patients.”
Availability of samples will determine in part which diseases the project will focus on. The researchers will probably choose three diseases, among them at least one common one, according to Hood.
He did not disclose the amount of funding for the project but said that “it’s quite substantial.”
The project is part of a larger collaboration between the government of Luxembourg, which is investing more than $200 million in the initiative; ISB; the Partnership for Personalized Medicine; and TGen. PricewaterhouseCoopers helped negotiate the deal.

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