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George Church Fielding X Prize Team; Says Sequencing Strategy May Combine Many Technologies

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George Church announced last week that his team plans to compete in the Archon Genomics X Prize competition, representing Harvard University's Wyss Institute.

Revealing his plans at the annual Consumer Genetics Conference in Boston, Church said his group hopes to use a "hybrid" of whatever the best technology is at the time the one-month, $10 million contest to sequence 100 genomes begins next fall.

The Wyss team is the second team to announce its participation, following Life Technologies' declaration earlier this year. Teams have until May 2013 to officially enter the competition, which will begin Sept. 5, 2013.

"I'm trying not to play favorites because I have so many offspring and friends in the field of sequencing technology, but we would like to represent one or more [platforms] at that time," Church said at the conference.

Indeed, it's hard to find a commercial sequencing firm without some connection to Church. According to his website, companies where Church is either a co-inventor or advisor include Azco Biotech, Danaher's Dover business, Complete Genomics, Intelligent Bio-Systems, Pacific Biosciences, Helicos BioSciences, Noblegen Biosciences, Genia Technologies, Ion Torrent, and Nabsys.

In an email to In Sequence, Church explained that his lab has been working most recently with three new sequencing approaches: an updated version of fluorescent in situ sequencing, long fragment read technology the team has developed in collaboration with Complete Genomics, and a tagged nanopore sequencing approach in collaboration with Genia.

At the conference, Church suggested that at least some of these recent efforts could play a role in the team's X Prize bid, but noted that his team is "not committing just yet" to any one technology or combination of technologies.

"We believe in hybrids of these various technologies [and] we are taking some of the best features of each of them," he said, mentioning FISS, Complete Genomics' LFR, and Genia's "incredible electronics for integrated circuits."

In his email, Church said his team plans to soon publish an update on its fluorescent in situ sequencing-by-synthesis approach, based on early work on cloning and amplifying DNA on glass microscope slides that the group published in Nucleic Acids Research in 1999.

At the conference, he said the method is applicable "not just for getting long reads, but for sequencing RNA in situ for heterogeneous cancers" or other complex tissues.

Last week, Church also announced a collaboration with Genia and researchers at Columbia University to integrate Genia's semiconductor platform with the Church team's polymerase fusion proteins and the Columbia researchers' Tag-based sequencing chemistry approach.

The NanoTag sequencing technology, licensed by Genia, was recently described in a proof-of-concept paper published online in Scientific Reports by the teams of Jingyue Ju at Columbia and John Kasianowicz at NIST (IS 10/2/2012)

In his presentation at the CGC conference, Church said the group estimates that the NanoTag sequencing method's error rate could be "better than" 10-8."

"That's not sequencing accuracy [now], that's analytical chemistry accuracy, but that could turn into sequencing accuracy," he said.

Church also highlighted a recent Nature paper on which he collaborated with Complete Genomics, describing a long fragment read method that enables whole-genome sequencing and haplotyping from 10 to 20 human cells with an error rate of one in 10 million bases (IS 7/17/2012).

Church was circumspect, however, on any precise plans for the X Prize competition. He said in his conference presentation that sequencing technologies are advancing rapidly and highlighted his group's lack of allegiance to any particular platform as an advantage in light of achievements that may be made between now and next fall.

"We might have a slight strategic advantage in that we can use virtually any combination of technologies, while a company is unlikely to use a competing method," he wrote to In Sequence.

Church said that since he is already "deeply involved" with any team likely to compete in the X Prize competition, he is "cheerleading for all of them."

At the conference he said that if the Wyss team wins, the group plans to donate the prize money to the Personal Genome Project, and hopes other teams would do the same.

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