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At OSU Conference, Hood Touts Family Sequencing as Way Forward for Personal Genomics

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By Turna Ray

COLUMBUS, Ohio — The future of personal genomics, according to Leroy Hood, is not in randomly sequencing individuals, but sequencing the genomes of entire families.

“Sequencing families is the key,” Hood, president of the Institute for Systems Biology, said at a conference hosted by Ohio State University's Center for Personalized Healthcare this week.

“It’s a waste of money to sequence random individuals,” Hood said, adding that family sequencing reduces the signal-to-noise ratio and lowers error the rate of sequencing studies, allowing for more efficient identification of candidate genes.

In order to illustrate his hypothesis, Hood said that his laboratory had sequenced the genomes of four members of a family — mother, father, and two children — to uncover candidate genes for two Mendelian diseases. He did not discuss the candidate genes or the diseases in detail. However, he noted that his team had identified 340,000 new SNPs from 4.2 million SNPs from the four genomes, and was able to narrow that down to three candidate genes for two diseases.

Hood’s team will be sequencing the genomes of more families, beginning in December and finishing in February. PGx Reporter's sister publication In Sequence reported last week that Complete Genomics — a startup offering sequencing services on its own next-generation sequencing technology — is providing the sequencing for this project [see In Sequence 09-29-2009].

Outside the US, ISB is already testing the family sequencing hypothesis on a larger scale with the University of Luxembourg. The partners last year announced a project to sequence 100 genomes from family members who have certain diseases

At the time, Hood spoke to In Sequence about the need to “push the whole business of sequence analysis to the next stage beyond just the SNP analyses that 23andMe and Navigenics are doing,” Hood described the collaboration with the University of Luxembourg as being “more along the lines of the 1,000 Genomes [Project], although we are going to be doing families rather than individuals." [see In Sequence 06-10-2008]

The family sequencing effort is just one piece in Hood’s armamentarium of projects using systems biology approaches to transform healthcare from being reactionary to being "predictive, preventive, personalized, and participatory," which he refers to as P4.

Also at the conference, Hood announced a partnership with OSU on the formation of the P4 Medical Institute, which aims to integrate the technical challenge of P4 medicine with societal challenges. The consortium will bring together academia and industry to develop “killer applications” to personalize healthcare.

“We want to take 100 patients, stratify them to 25, and say here’s the therapy that will give you a 98-percent cure rate. That’s the kind of killer applications we’re thinking about,” Hood said.

Under the partnership, OSU will model demonstration projects using these predictive applications in chronic and acute diseases. He added that in addition to OSU, P4 MI is also speaking with three potential industry partners. He did not name the interested commercial firms.

At the conference, Hood discussed several other projects he is involved in. ISB has launched a new platform company, called Integrated Diagnostics, which will use organ-specific blood protein fingerprints to develop diagnostic platforms and create protein-capture agents. Hood said his team had identified 88 organ-specific blood proteins.

Hood’s group is also working with Jim Heath of Caltech to develop a microfluidic protein chip that will allow researchers to make organ-specific protein measurements from a droplet of blood. The organ-specific blood protein fingerprint strategy and the protein chip under development, Hood hopes, will allow for the early prediction of diseases and become a cornerstone of P4 medicine.

The government of Luxembourg last year also began working with ISB, the Partnership for Personalized Medicine led by Lee Hartwell, and Arizona's Translational Genomics Research Institute led by Jeffrey Trent, to build the state’s biobanking effort, establish the Center for Systems Biology Luxembourg, and develop a gene-based lung cancer diagnostic [see PGx Reporter 06-18-2008].

However, Lee noted at the conference that the actualization of P4 medicine will require scientific advancements toward complete sequencing of single cells; the digitization of healthcare; global partnerships to tackle healthcare problems; and the education of physicians and patients.

“Society is facing in biological sciences six or seven really big problems that if you can put together globally integrated approaches you can be infinitely more efficient than” is currently possible, Hood said.

Hood acknowledged that he has faced barriers to the acceptance of the P4 medicine paradigm, particularly when it comes to educating physicians. “I’ve now gone to four medical schools pitching this idea that we could create an Institute for Systems Medicine and … the basic reaction I would surmise by saying, there is enormous arrogance that’s associated with excellence,” he said.

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