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January 13, 2010

Genone Sequencing Costs and Projects

Illumina Inc. unveiled new technology it says can sequence a person's entire genetic code for under $10,000.

Illumina also said that 128 of its new sequencing systems, called the HiSeq 2000, had been purchased by BGI, formerly known as Beijing Geonomis Institute, which will install most of the machines in a new genome center in Hong Kong. Illumina said the machines will list for $690,000 each before volume discounts.

The new technology is the latest offering in an intense race among companies that make the machines to reduce the time it takes to decode a person's genome and to make it more affordable for use in both drug development and eventually patient medical care.

Other sequencing companies include Pacific Biosciences Inc., Life Technologies Inc. and Helicos Biosciences Inc.

Mr. Flatley said the HiSeq 2000 can run two genomes at once and complete the entire sequence of 3.1 billion pieces of information, called base-pairs, within seven or eight days.

Running two genomes at once, he said, will enable researchers to run a person's genome at the same time it runs, for instance, the genome of a cancer tumor taken from the same person


2. The National Human Genome Research Institute (NHGRI) has awarded more than $113 million provided by the American Recovery and Reinvestment Act. The new awards, added to NHGRI's regularly appropriated $367 million budget, will stimulate ground-breaking research ranging from studies aimed at understanding the human genome to those intended to lead to improvements in the prevention, diagnosis and treatment of human illness.

Under the Recovery Act, two-year awards have been made to seven investigator teams to develop revolutionary sequencing technologies.







* Mark Akeson, Ph.D., University of California Santa Cruz
Controlling Large DNA Fragments During Nanopore Sequencing
$1.1 million

* George Church, Ph.D., Harvard University, Cambridge, Mass.
Development of Electron Microscopy-Based Nucleic Acid Polymer Sequencing
$2.5 million

* Ronald Davis, Ph.D., Stanford University, Stanford, Calif.
A Strategy for High Quality Clinical Resequencing of the Human Genome
$2.8 million

* Stuart Lindsay, Ph.D., Arizona State University, Tempe, Ariz.
Carbon Nanotubes: A New Synthetic Nanopore for Sequencing
$1.7 million

* John Thompson, Ph.D. Helicos Biosciences, Cambridge, Mass.
Providing the $1,000 Genome via Improved Single Molecule Sequencing
$2.9 million

* Stephen Turner, Ph.D., Pacific Biosciences, Menlo Park, Calif.
Direct Single Base-Pair Real-Time DNA Methylation Sequencing
$1.2 million

* X. Sunney Xie, Ph.D., Harvard University, Cambridge, Mass.
Single Cell Single Molecule Digital mRNA Profiling with No PCR Amplification
$1.2 million

So several possibilities for sub-$1000 genome sequencing in 2011. Pacific Biosciences could release a sequencing product in and around the $1000 price range in 2010.

3. Pacific Biosciences has a Single Molecule Real-Time (SMRT) DNA sequencing, due to be released commercially in 2010 and could enable $100 genome sequencing in 15 minutes in 2013. The second generation real time DNA reader in 2013 is the one that is expected to hit the $100 genome sequencing price. They will release a product in 2010 but it will not be that cheap.

MIT Technology Rreview reported on BioNanomatrix. Bionanomatrix is pursuing what many believe to be the key to personalized medicine: sequencing technology so fast and cheap that an entire human genome can be read in eight hours for $100 or less.

BioNanomatrix believes it can reach the $100 target in five years (2014). The reason for its optimism: company founder Han Cao has created a chip that uses nanofluidics and a series of branching, ever-narrowin­g channels to allow researchers, for the first time, to isolate and image very long strands of individual DNA molecules.

If the company succeeds, a physician could biopsy a cancer patient's tumor, sequence all its DNA, and use that information to determine a prognosis and prescribe treatment-- all for less than the cost of a chest x-ray.

Cao's chip, which neatly aligns DNA, is essential to cheaper sequencing because double-stranded DNA, when left to its own devices, winds itself up into tight balls that are impossible to analyze. To sequence even the smallest chromosomes, researchers have had to chop the DNA up into millions of smaller pieces, anywhere from 100 to 1,000 base pairs long. These shorter strands can be sequenced easily, but the data must be pieced back together like a jigsaw puzzle. The approach is expensive and time consuming. What's more, it becomes problematic when the puzzle is as large as the human genome, which consists of about three billion pairs of nucleo­tides. Even with the most elegant algorithms, some pieces get counted multiple times, while others are omitted completely. The resulting sequence may not include the data most relevant to a particular disease.

In contrast, Cao's chip untangles stretches of delicate double-stranded DNA molecules up to 1,000,000 base pairs long--a feat that researchers had previously thought impossible. The series of branching channels gently prompts the molecules to relax a bit more at each fork, while also acting as a floodgate to help distribute them evenly. A mild electrical charge drives them through the chip, ultimately coaxing them into spaces that are less than 100 nanometers wide. With tens of thousands of channels side by side, the chip allows an entire human genome to flow through in about 10 minutes. The data must still be pieced together, but the puzzle is much smaller (imagine a jigsaw puzzle of roughly 100 pieces versus 10,000), leaving far less room for error.

The chip meets only half the $100-genome challenge: it unravels DNA but does not sequence it. To achieve that, the company is working with Silicon Valley-based Complete Genomics, which has developed bright, fluorescently labeled probes that bind to the 4,096 possible combinations of six-letter DNA "words." Along with ­BioNanomatrix's chip, the probes could achieve the lightning-fast sequencing necessary for the $100 genome. But the probes can't stick to double-stranded DNA, so Complete Genomics will need to figure out how to open up small sections of DNA without uncoupling the entire molecule.
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