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BRANFORD, Conn.—IBM launched itself into the sequencing market in life sciences in a big way in late 2009 with the announcement of its DNA Transistor technology and the prediction that it might not just usher in the age of the $1,000 genome, but perhaps bring that price down to three-figure levels in the forseeable future. Now the Armonk, N.Y.-based information technology powerhouse is being joined in that effort by Swiss-headquartered pharmaceutical and diagnostics giant Roche and its Connecticut-based sequencing subsidiary, 454 Life Sciences.

Under the agreement, Roche and IBM will develop a nanopore-based sequencer designed to directly read and decode human DNA quickly and efficiently. In advancing IBM's promising but fledgling DNA Transistor technology, the collaboration will take advantage of IBM's leadership in microelectronics, information technology and computational biology and Roche's expertise in medical diagnostics and genome sequencing.

The novel technology that was developed by IBM Research has been called a "DNA bar code reader" by some market watchers, because it offers single-molecule sequencing by decoding molecules of DNA as they are threaded through a nanometer-sized pore in a silicon chip.

It was a logical fit for Roche and IBM to come together in refining the technology, because Roche and its 454 subsidiary offer the longest read lengths right now with their next-generation sequencing platforms, notes Dr. Ulrich Schwoerer, head of global marketing for 454 Life Sciences Corp. "We also have a lot of experience with next-gen technology and taking it to market, and we are the world's largest biotech and diagnostics company."

Schwoerer notes that the value and power of the DNA Transistor technology has been proven in the lab, but now, "it's time to prove it in vivo," he says. "The most important challenge in nanopore sequencing is to slow down the movement of the DNA molecule through the pore, because that is what will control the quality of the read."

IBM, for all its research ability and technical skill—and its ability to advance life sciences through computational breakthroughs—needs a partner with a strong set of skills in life sciences, notes Dr. Gustavo Stolovitzky, manager of functional genomics and systems biology at IBM. "This is the right time to do this kind of research and get this kind of sequencing ability on the market," he says. "We realize that the right technology to make that happen might be found by someone else, so we needed to play the range. Roche has the sequencing expertise and knowledge of biochemistry and biology that we don't, and a track record in first- and second-generation sequencing technology, so they are an ideal partner for us on this. Likewise, they rely on us for skills in areas like nanotechnology."

As part of the agreement, Roche will fund the continued development of the technology at IBM and provide additional resources and expertise through collaboration with its subsidiary 454 Life Sciences. Roche will develop and market all products based on the technology.

According to Roche, its investment in future genomic technologies builds upon the strength of its currently available 454 Sequencing Systems, which generate hundreds of thousands of long, high-quality sequencing reads in hours. The technology is available for large-scale genomic analysis with the GS FLX System and for benchtop sequencing with the GS Junior System. Roche maintains that its 454 Sequencing Systems are "poised to be first next-generation sequencing technology to move from the laboratory to the clinic." Ultimately, Roche and IBM say, the DNA Transistor technology has the potential to improve throughput and reduce costs to achieve the vision of whole human genome sequencing at a cost of between $100 and $1,000.

"Sequencing is an increasingly critical tool for personalized healthcare. It can provide the individual genetic information necessary for the effective diagnosis and targeted treatment of diseases," explained Manfred Baier, head of Roche Applied Science, in an official announcement about the deal. "We are confident that this powerful technology—plus the combined strengths of IBM and Roche—will make low-cost whole genome sequencing and its benefits available to the marketplace faster than previously thought possible."

Having access to an individual's personal genetic code could, of course, advance the quality of medical care by identifying persons who will gain the greatest benefit from a particular medicine and those who are at most risk of adverse reaction, as well as enhance the ability of companies to better develop and test their drugs.

"By merging computational biology, biotechnology, and nanotechnology skills, we are moving closer to producing a system that can quickly and accurately translate DNA into medically-relevant genetic information," said Ajay Royyuru, senior manager of the Computational Biology Department at IBM Research, in the news release about the deal. "The challenge of all nanopore-based sequencing technologies is to slow and control the motion of the DNA through the nanopore. We are developing the technology to achieve this so that the reader can accurately decode the DNA sequence."

454 Life Sciences' Schwoerer notes that IBM and Roche are the trailblazers in this area, and quite probably on the right track to make personalized genomics sequencing a reality soon. "Oxford Nanopore recently announced that they plan to switch from using a natural nanopore to using an artificial nanopore surface, just like we and IBM are doing," he notes. "An artificial surface is far more efficient and can pack more densely than a natural surface, and they are only just realizing that, while we already knew it. We've been working on nanopores like this for years, and realized the potential of them quite early."



IBM partners with University of Missouri on Genomics Research Initiative

COLUMBIA, Mo.—IBM and the University of Missouri announced July 2 a life sciences research initiative using IBM high-performance computing technologies to advance the school's bioinformatics research projects. The goal of the initiative is to develop a first-of-a-kind cloud computing environment for genomics research collaboration at a regional level.

Mizzou researchers are pursuing projects aimed at fighting the spread of infectious diseases such as malaria and H1N1, as well as a number of projects involving the study of genome sequences in plants and animals to help improve the quality and quantity of food production. For example, Mizzou researchers are studying bovine genes in hopes of increasing reproductive efficiency in livestock and looking at ways to grow corn in drought conditions.

The development of a genomics cloud also would have a significant impact on the way patients are diagnosed, because it would, as the university and IBM say, "bring human genome sequencing and analysis into a clinical setting for the first time, putting a valuable new tool into the hands of medical professionals and enabling a more personalized approach to medicine."

"This collaboration with IBM provides our researchers, and those being trained to become tomorrow's researchers and educators, access to critical high-performance computing resources needed to process massive data sets and apply increasingly more sophisticated bioinformatics tools and technologies," says Gordon Springer, associate professor in the University of Missouri Computer Science Department and scientific director of the University of Missouri Bioinformatics Consortium.

In the first phase of the project, IBM will provide Mizzou with an IBM iDataPlex high-performance computing system, along with related software, that will integrate with the university's existing computing infrastructure to significantly speed the process of DNA sequencing and analysis of humans, plants and animals. The iDataPlex will also be used to collect and store the massive amounts of data that result from that work, providing Mizzou researchers with more reference points.

The second phase will involve University of Missouri and IBM working together to create a prototype cloud computing environment for genomics research, followed by a final phase in which the genomics cloud would become fully operational and be expanded to a regional domain. This first-of-a-kind cloud would allow sharing of bioinformatics resources among universities and institutions across a larger geographic area, which could potentially lead to a "Life Sciences Corridor" across Missouri and Kansas, and throughout the Midwest.

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