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Bucking Trend, Newbie Genome Corp. Sticks to Sanger

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A new DNA sequencing startup is swimming against the tide: While most next-generation sequencing platforms combine new chemistries, short reads, and miniaturization, Genome Corp. is betting on factory-style Sanger dideoxy sequencing and read lengths of at least 1,200 base pairs to make sequencing faster and more affordable.

The Providence, RI-based startup believes its approach, which it calls “massively parallel” Sanger sequencing, will be competitive with existing next-generation technologies.

“I realized that if you do a few things to Sanger [sequencing], that it should outcompete and outperform all these other technologies” in cost, throughput, and accuracy, says Kevin Ulmer, who co-founded Genome Corp. and serves as its president and chief scientific officer (and, currently, its only full-time employee). The company succeeds another firm called Really Tiny Stuff, which Ulmer founded in 2002 to develop the sequencing technology.

So does the future lie in Sanger sequencing? “We see no reason to abandon it, and many reasons to want to keep it,” Ulmer says, pointing to the technology’s long reads and its well-understood chemistry and error properties.

But while he plans to keep Sanger’s dideoxy sequencing chemistry and fluorescent dyes, he wants to make a number of changes to the current technology, starting with the sample prep: Ulmer wants to produce tens of millions of Sanger reads in a single reaction tube.

He also plans to build a sequencing “factory” that transforms the electrophoresis and imaging into “an industrial-scale continuous process” and increases the read length to beyond 1,200 base pairs. “Envision something that looks more like the printing press that prints your Sunday newspaper rather than a roomful of desktop printers,” Ulmer says.

He declined to provide details of how this approach will increase the throughput and lower the cost, other than to say that every aspect, starting from sample prep to genome assembly, will be optimized.

— Julia Karow

Short reads

Researchers published in Science the genome sequence of Giardia lamblia, a water-borne parasite that causes intestinal illness in humans. Led by scientists at the Marine Biological Laboratory in Woods Hole, Mass., the project found that the organism’s genome has fewer genetic components than most other eukaryotes.

The J. Craig Venter Institute plans to resequence Craig Venter’s genome using Applied Biosystems’ new SOLiD platform. It will also embark on large-scale human resequencing with a goal of reaching 10,000 genomes in the next decade, starting with 10 to 30 individuals in 2008. The technology for that project has not yet been decided.

Perlegen and 454 Life Sciences will collaborate on a project to resequence “hundreds” of human DNA samples with the goal of developing a test to predict how patients will respond to a certain class of drug. Under the agreement, the companies will resequence portions of genomes from patient samples using 454 sequencing and Perlegen’s sample-prep and amplification technologies.

An international team of researchers led by the Joint Genome Institute; the University of California, Los Angeles; and the Carnegie Institution sequenced the genome of Chlamydomonas reinhardtii, a green algae used as a model system for the study of photosynthesis and cell motility.

Patents

US Patent 7,283,912. DNA probe design device and information processing method for DNA probe design. Inventors: Hiroto Yoshii and Toshifumi Fukui. Assignee: Canon Kabushiki Kaisha. Issued: October 16, 2007.

This invention relates to studies of partial base sequences, which are analyzed for target bases and held in frequency tables. Those tables are then “displayed so as to be comparable with reference to the partial base sequences, and at least one of the plurality of partial base sequences is determined according to instruction operations made by a user, thereby forming probe candidates based on the determined partial base sequences.”

US Patent 7,272,507. Applications of parallel genomic analysis. Inventor: Michael Paul Strathmann. Issued: September 18, 2007.

According to the abstract, “the present invention provides parallel methods for determining nucleotide sequences of polynucleotides associated with sample tags. Applications of sequence information acquired by these methods are also provided.”

Data point

$8.8 million

BioNanomatrix and Complete Genomics formed a joint venture that will share a five-year, $8.8 million grant from the US National Institute of Standards and Technology to develop technology that will be able to sequence a human genome in eight hours for less than $100.

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