Roche and IBM Collaborate to Develop Nanopore-Based DNA Sequencing Technology

Collaboration aims to accelerate human genome analysis and enable advancements
in personalized healthcare.
YORKTOWN HEIGHTS, N.Y. & BRANFORD, Conn.–(Business Wire)–
Roche (SWX:RO)(SWX:ROG)(Pink Sheets: RHHBY) and IBM (NYSE: IBM) announced today
an agreement to develop a nanopore-based sequencer that will directly read and
decode human DNA quickly and efficiently. Focused on advancing IBM`s recently
published “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, developed by IBM Research, offers true single molecule
sequencing by decoding molecules of DNA as they are threaded through a
nanometer-sized pore in a silicon chip. The approach holds the promise of
significant advantages in cost, throughput, scalability, and speed compared to
sequencing technologies currently available or in development.

“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. “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.”

Ultimately, the technology has the potential to improve throughput and reduce
costs to achieve the vision of whole human genome sequencing at a cost of $100
to $1,000. Having access to an individual`s personal genetic code could 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.

“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. “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.”

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

Roche`s 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. Shown to provide significant
medical value in targeted resequencing applications for virology and oncology
research, 454 Sequencing Systems are poised to be first next-generation
sequencing technology to move from the laboratory to the clinic.

For more information on 454 Sequencing Systems, visit www.454.com.

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused
healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is
the world`s largest biotech company with truly differentiated medicines in
oncology, virology, inflammation, metabolism and CNS. Roche is also the world
leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in
diabetes management. Roche`s personalised healthcare strategy aims at providing
medicines and diagnostic tools that enable tangible improvements in the health,
quality of life and survival of patients. In 2009, Roche had over 80`000
employees worldwide and invested almost 10 billion Swiss francs in R&D. The
Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a
wholly owned member of the Roche Group. Roche has a majority stake in Chugai
Pharmaceutical, Japan. For more information: www.roche.com.

About IBM
For more information, visit www.ibm.com/smarterplanet

For life science research only. Not for use in diagnostic procedures.

454, 454 SEQUENCING, 454 LIFE SCIENCES, GS FLX and GS JUNIOR are trademarks of
Roche.

IBM is a registered trademark of International Business Machines Corporation in
the United States, other countries, or both.

Roche Diagnostics
Dr. Burkhard Ziebolz
Phone: +49 8856 604830
Email: burkhard.ziebolz@roche.com
or
454 Life Sciences Corporation, a Roche Company
Dr. Ulrich Schwoerer
Phone: +1 203 871 2300
Email: ulrich.schwoerer@roche.com
or
IBM
Michael Loughran
Phone: +1 914 945 1613
Email: mloughra@us.ibm.com

Copyright Business Wire 2010

Burning bush plant promises low-cal vegetable oil, biofuels

Washington, May 21 (ANI): New genetic discoveries from a shrub called the burning bush, known for its brilliant red fall foliage, could pave the way for new advances in biofuels and low-calorie food oils, found Michigan State University scientists.

New low-cost DNA sequencing technology applied to seeds of the species Euonymus alatus – a common ornamental planting – was crucial to identifying the gene responsible for its manufacture of a novel, high-quality oil.

However, despite its name, the burning bush is not a suitable oil crop.

Yet inserted into the mustard weed – well known to researchers as Arabidopsis and a cousin to commercial oilseed canola – the burning bush gene encodes an enzyme that produces a substantial yield of unusual compounds called acetyl glycerides, or acTAGs.

Related vegetable oils are the basis of the world’s oilseed industry for the food and biofuels markets, but the oil produced by the burning bush enzyme claims unique and valuable characteristics.

One is its lower viscosity, or thickness.

“The high viscosity of most plant oils prevents their direct use in diesel engines, so the oil must be converted to biodiesel. We demonstrated that acTAGs possess lower viscosity than regular plant oils. The lower viscosity acTAGs could therefore be useful as a direct-use biofuel for many diesel engines,” explained Timothy Durrett.

He said that its improved low-temperature characteristics could also make it suitable for diesel fuel.

And acTAGs boast lower calorie content than other vegetable oils,“thus they could be used as a reduced-calorie food oil substitute,” added Durrett.

The researchers now are working to improve the modified mustard weed seeds’ acTAGs yield and already report purity levels of up to 80 percent.

“It should now be possible to produce acetyl glycerides in transgenic oilseed crops or single cell production systems such as algae that are the focus of much current effort in biofuels research. With the basic genetics defined and thus one major technical risk greatly reduced, the way is open to produce and assess this novel oil in food and nonfood applications,” said Pollard.

The study was published in the latest issue of Proceedings of the National Academy of Sciences. (ANI)

New method to make DNA sequencing faster and cheaper

Washington, May 20 (ANI): Boston University biomedical engineers have developed a new method to make DNA sequencing a lot faster and cheaper – and thus closer to routine use in clinical diagnostics.

The team has demonstrated the first use of solid state nanopores — tiny holes in silicon chips that detect DNA molecules as they pass through the pore — to read the identity of the four nucleotides that encode each DNA molecule.

“We have employed, for the first time, an optically-based method for DNA sequence readout combined with the nanopore system,” said Boston University biomedical engineer Amit Meller, who collaborated with other researchers at Boston University, and at the University of Massachusetts Medical School in Worcester. “This allows us to probe multiple pores simultaneously using a single fast digital camera. Thus our method can be scaled up vastly, allowing us to obtain unprecedented DNA sequencing throughput.”

The discovery could lead to major advances in drug development, preventative medicine and personalized medicine.

The new nanopore method does not rely on enzymes whose activity limits the rate at which DNA sequences can be read.

“This puts us in the unique advantageous position of being able to claim that our sequencing method is as fast as the rapidly evolving photographic technologies,” said Meller. “We currently have the capability of reading out about 200 bases per second, which is already much faster than other commercial third-generation methods. This is only the starting point for us, and we expect to increase this rate by up to a factor of four in the next year.”

“I believe that it will take three to five years to bring cheap DNA sequencing to the medical marketplace, assuming an aggressive research and development program is in place,” said Meller.

The research is detailed in Nano Letters. (ANI)

New rat study may help understand genetic basis of human hypertension

Washington, April 29 (ANI): Scientists have sequenced the genome of the spontaneously hypertensive rat, which could help understand causes of the disease in humans.

The spontaneously hypertensive rat (SHR) strain is the most widely studied animal model of human hypertension. Research on this strain has identified many genomic regions that likely harbour genetic variants that are responsible for the hypertension phenotype, however without a complete sequence of the hypertensive rat genome, it has been difficult to resolve many of these genomic changes and explore their molecular consequences.

Taking advantage of new technologies that are rapidly driving down the cost of DNA sequencing, an international team of researchers led by Timothy Aitman of the MRC Clinical Sciences Centre and Imperial College London have sequenced the first genome of a mammalian disease model with second-generation sequencing technology.

By comparing the SHR genome sequence with that of the rat reference genome sequence, Aitman and colleagues generated a nearly complete catalog of SHR genomic variants that could contribute to hypertension and other phenotypes.

They also found that genes known to be abnormally expressed in SHR are especially enriched for sequence variants.

The group expected that the genome sequence would reveal mutations disrupting a number of genes in the SHR strain, however the number of mutated genes they found was quite surprising – 788 genes are mutated in SHR compared to the reference genome, including 60 that are deleted altogether.

“So many major differences in protein sequence were unexpected because of the previous belief that differences in a small number of genes and proteins would be responsible for the phenotypic differences between such rat strains,” said Aitman.

Of the 788 mutated genes identified in the SHR genome, many are related to cellular functions such as ion transport and plasma membrane localization, as well as immunological and neurological processes.

The authors suggest that defects in these functional categories may be causally associated with the known phenotypes of this strain.

Aitman said that their characterization of genetic variation in the hypertensive rat would be invaluable for complete elucidation of the causes of hypertension and related traits at the molecular level in hypertensive rat.

“This in turn will pave the way for greater understanding of the genetic basis of hypertension in humans,” Aitman said.

The study has been published online in Genome Research. (ANI)

Discovery of millions of new microbes opens ”huge frontier” in science

London, April 19 (ANI): Scientists have discovered millions of tiny microbes, hitherto unknown to science, at the bottom of the sea.

These organisms include microbes of bacteria, worms and ocean insects less than 1mm long.

Scientists made the path-breaking discovery using technology such as DNA sequencing, that allows researchers to differentiate between different species, and submarines that can be operated thousands of feet under the sea.

A survey was conducted as part of a 10-year international project to find out more about the oceans, the Census of Marine Life.

For one study, ocean samples were gathered from over 1,200 sites around the world to find out more about microbial life.

It discovered microbes with 18 million different DNA sequences, suggesting the presence of millions of yet unknown species.

Another project found 7,000 new genus of bacteria in the Western English Channel alone.

Nearly 3,000 types of bacteria were found in a sponge from Australia”s Great Barrier Reef.

The findings of the survey have led scientists to believe that there could be a billion microbial cells in every litre of seawater.

A separate study of holozooplankton, that look like tiny transparent insects, increased the number of known species to 14,000 from 7,000.

A study into roundworms found 500,0000 in a single square metre of ocean floor, while currently there are 16,000 known species of seaworms.

John Baross of the University of Washington, a contributor to the census, said the findings would open up new doors in science that could help understand changes in the food chain, weather patterns and carbon cycles.

“Marine animals alone may account for hundreds of millions microbial species. This is a huge frontier for next decade,” the Telegraph quoted him as saying. (ANI)

Discovery of millions of new microbes opens ”huge frontier” in science

London, April 19 (ANI): Scientists have discovered millions of tiny microbes, hitherto unknown to science, at the bottom of the sea.

These organisms include microbes of bacteria, worms and ocean insects less than 1mm long.

Scientists made the path-breaking discovery using technology such as DNA sequencing, that allows researchers to differentiate between different species, and submarines that can be operated thousands of feet under the sea.

A survey was conducted as part of a 10-year international project to find out more about the oceans, the Census of Marine Life.

For one study, ocean samples were gathered from over 1,200 sites around the world to find out more about microbial life.

It discovered microbes with 18 million different DNA sequences, suggesting the presence of millions of yet unknown species.

Another project found 7,000 new genus of bacteria in the Western English Channel alone.

Nearly 3,000 types of bacteria were found in a sponge from Australia”s Great Barrier Reef.

The findings of the survey have led scientists to believe that there could be a billion microbial cells in every litre of seawater.

A separate study of holozooplankton, that look like tiny transparent insects, increased the number of known species to 14,000 from 7,000.

A study into roundworms found 500,0000 in a single square metre of ocean floor, while currently there are 16,000 known species of seaworms.

John Baross of the University of Washington, a contributor to the census, said the findings would open up new doors in science that could help understand changes in the food chain, weather patterns and carbon cycles.

“Marine animals alone may account for hundreds of millions microbial species. This is a huge frontier for next decade,” the Telegraph quoted him as saying. (ANI)

Bugs on a person’s hand can act like fingerprints to nab criminals

London, March 16 (ANI): Scientists have said that by comparing the unique collection of bacteria found on a person’s hand to those recovered at a crime scene, microbes could act like fingerprints to nab the culprit.

Our fingers are home to a unique collection of bacteria that get left on surfaces we touch.

According to a report in New Scientist, by comparing bugs found on a person’s hand to those recovered at a crime scene, you might be able identify the perpetrator.

“There are certain situations where human DNA analysis or standard fingerprinting doesn’t work, maybe this is just another tool,” said Noah Fierer, a microbiologist at the University of Colorado in Boulder.

His team knew that microbial communities on skin tend to be unique to the individual and change little over time.

To see if these qualities could be applied to forensics, his team swabbed several computer keyboards and the fingertips of their users, then identified about 1400 different kinds of bacteria living on each, using DNA sequencing.

The keyboard bacteria closely matched their owner’s fingertips.

In another test, Fierer’s team were able to correctly match nine computer mice with their owners.

The “microbeprint” seems to be long-lasting: swabs left at room temperature for two weeks could be matched to their owners.

“But accuracy issues mean you won’t see them used in court just yet,” Fierer said. (ANI)

Counting duplicated genome segments now possible with new computational method

London, August 31 (ANI): Counting copies of duplicated genome sequences and doing initial analyses of their contents are possible with the aid of a new computational method, according to a study.

Led by scientists at the University of Washington (UW), the study suggests that the number of copies of particular DNA segments can differ from one person to the next.

The researchers use the term mrFAST, an acronym for micro-read Fast Alignment Search Tool, to refer to the novel method.

In their study report, they have highlighted the fact that segmental duplications in the human genome have been associated with susceptibility and resistance to disease.

The report points out that duplicated segments have been linked to such disorders as lupus, Crohn’s disease, mental retardation, schizophrenia, colour blindness, psoriasis, and age-related macular degeneration.

It adds that segmental duplications often contain duplicated genes, many of which have an unknown function, and that individuals have different numbers of copies of some of these duplications.

The researchers write that determining the number, content, and location of segmental duplications is an important step in understanding the health significance of gene copy-number variation.

“New computational methods, combined with next-generation DNA sequencing technology, has provided for the first time an accurate census of specific genes that exist in varying number of copies,” Nature magazine quoted Alkan as saying.

“This is a way to deal with some of the most complex regions of the human genome and do what might appear to be a simple thing: Count whether a person has one, two, three or more copies of a gene. In fact, such counting is surprisingly difficult,” said Kidd.

The researchers say that next-generation technology for sequencing the human genome has far greater detection power, and costs substantially less than the traditional sequencing method known as Sanger sequencing.

According to them, the new technologies are beginning to distinguish subtle dissimilarities between nearly identical gene copies.

“This can provide researchers with a more accurate assessment of specific gene content and insight into functional constraints,” Alkan said.

“The newer, faster genome sequencing platforms may eventually make it feasible to detect the full-spectrum of genomic variation among many individuals, including patients suffering from diseases of genetic origin. Next-generation technology and computational methods promise low cost, rapid sequencing of different individuals and may lead to a fuller understanding of the patterns and significance of human genetic variation,” Alkan added.

The analytical method they devised is already being tapped for the 1000 Genome Project, an international effort to catalog and compare the genomes of hundreds of people from around the world.

Alkan, Kidd, and their colleagues note that the ability to accurately and systematically determine the absolute copy number for any genomic segment is a notable step toward a true and complete picture of individual genomes, and how the genome shapes a person’s characteristics.

“The next challenge will be defining variation in the sequence content and the structural organization of these dynamic and important regions of the human genome,” they wrote.

A research article describing their study has been published in the journal Nature Genetics. (ANI)

New biomarkers of melanoma identified

Washington, June 30 (ANI): Scientists from Yale University have identified new biomarkers that will help develop more effective treatment strategies to fight melanoma, the most serious form of skin cancer.

The research team has mapped chemical modifications of DNA in the melanoma genome that will open new avenues for developing improved therapies.

In addition to mutations to the DNA code that can cause malignancies, epigenetic changes – alterations to the chemical modifications of DNA that regulate genes – are frequent in a number of diseases, including cancer.

If the normal epigenetic patterns that regulate gene expression are disrupted, cellular functions can go awry and lead to disease.

Lead researchers Dr Ruth Halaban and Dr Sherman Weissman of Yale University investigated genome-wide epigenetic changes, termed DNA methylation, in melanoma cells.

“This is of particular importance in melanomas, because a major etiological factor is sun exposure,” Halaban said, explaining that inflammation and reactive oxygen species caused by the sun can produce epigenetic changes and mutations.

Halaban added that because DNA methylation can be reversed, it is an attractive target for cancer therapy.

The team then focused on five genes in particular, three of which had not been implicated in melanoma until now.

In clinical specimens, methylation of these promoters was predominantly detected in advanced-stage tumors, suggesting that these markers will be useful for monitoring tumour progression.

Furthermore, they found that by treating melanoma cells with a drug called decitabine, an inhibitor of DNA methylation, these genes could be reactivated.

Halaban suggests that by combining their method for finding methylation markers with the latest DNA sequencing technologies, researchers will be able to uncover genes where an interaction between genetic mutations and epigenetic changes play a role in the development of melanoma, and perhaps other cancers.

With this information, researchers can devise even more effective strategies to combat the disease.

The study is published in Genome Research. (ANI)

Our skin hosts much more diverse set of bacteria than previously believed

Washington, May 29 (ANI): Human skin is home to a much wider array of bacteria than previously thought, a new study by National Institutes of Health researchers has shown.

The study has also shown that at least among healthy people, the greatest influence on bacterial diversity appears to be body location. For example, the bacteria under one person’s arms could be more similar to those under another person’s arm than they are to the bacteria that live on your forearm.

These variations in bacterial habitats may explain why some skin complaints tend to affect certain areas of the body.

“Our work has laid an essential foundation for researchers who are working to develop new and better strategies for treating and preventing skin diseases,” said Julia A. Segre, Ph.D., of the National Human Genome Research Institute (NHGRI), who was the study’s senior author.

“The data generated by our study are freely available to scientists around the world. We hope this will speed efforts to understand the complex genetic and environmental factors involved in eczema, psoriasis, acne, antibiotic-resistant infections and many other disorders affecting the skin,” Segre added.

Drawing on the power of modern DNA sequencing technology and computational analysis, the research team from NHGRI, the National Cancer Institute (NCI) and the NIH Clinical Center uncovered a far more diverse collection of microbes on human skin than had been detected by traditional methods that involved growing microbial samples in the laboratory.

The study involved taking skin samples from 20 sites on the bodies of 10 healthy volunteers.

Study co-author Maria L. Turner, M.D., senior clinician in NCI’s Dermatology Branch, said: “We selected skin sites predisposed to certain dermatological disorders in which microbes have long been thought to play a role in disease activity.”

The researchers extracted DNA from each sample and sequenced the 16S ribosomal RNA genes, which are a type of gene that is specific to bacteria.

The researchers identified more than 112,000 bacterial gene sequences, which they then classified and compared. The analysis detected bacteria belonging to 19 different phyla and 205 different genera, with diversity at the species level being much greater than expected.

To gauge how much the skin microbiome differs among healthy people, the researchers studied many different parameters.

They found considerable variation in the number of bacteria species at different sites, with the most diversity being seen on the forearm (44 species on average) and the least diversity behind the ear (19 species on average).

The study was published today in the journal Science. (ANI)

Quantum tunneling may aid quest for low-cost DNA sequencing

Washington, March 23 (ANI): A new research has indicated that a ghostly property of matter, called quantum tunneling, may aid the quest for accurate, low-cost DNA sequencing and sensor applications.

Stuart Lindsay and his collaborators at the Biodesign Institute of Arizona State University have done the research.

Tunneling implies that a particle, say an electron, can cross a barrier, when, according to classical physics, it does not have enough energy to do so.

Unraveling the DNA sequences of the human genome a decade ago was a remarkable achievement.

Today, the task of sequencing some 3 billion chemical base pairs of the genome, enough information to fill a 20-volume encyclopedia, remains a daunting challenge, thus far accomplished largely through brute force means.

But, such methods are typically slow and extravagantly expensive.

Stuart Lindsay’s technique for observing DNA sequences relies on devices known as scanning tunneling- (STM) and atomic force- (ATM) microscopes.

He exploits these sensitive instruments to identify complementary DNA base pairs, evaluating the hydrogen bonds formed between them.

Base pairing rules for DNA dictate that the hydrogen bonds work to join up appropriate nucleotide pairs like jigsaw pieces-adenine with thymine and cytosine with guanine.

The scanning tunneling microscope used in the present study features a delicate electrode tip held very close to the DNA sample.

When this tip is fitted with a particular nucleotide and brought in contact with its complementary mate-embedded in the substrate, the hydrogen bonds stick the bases together and they attach, like tiny magnets.

As Lindsay describes the method, “You have sensing chemicals attached to one electrode and the target you want to sense attached to another one. When the junction spontaneously self-assembles, you get a signal. It’s a new way of doing recognition at the atomic scale.”

Now, Lindsay’s research team has developed a method to identify different DNA base pairs, which could serve as the foundation for a new DNA sequencing technology.

“The tunnel current is there as a readout of how long that molecular pair survived in the junction,” Lindsay said. “But, it turns out that it’s an incredibly nice way of identifying which molecular pair it was,” he added.

Although quantum tunneling seems exotic, Lindsay points out that the routine leaking of electrons from one atom to another to form a chemical bond is a similar process.

If significant challenges to reading single molecules through such a technique can be overcome, the method holds the potential for inexpensive DNA sequencing, operating at the breakneck pace of thousands of base pairs per second. (ANI)

Finding ‘shadow life’ on Earth may help scientists discover extraterrestrial life

London, March 14 (ANI): By searching for an alternative form of microbial life on Earth, dubbed ‘shadow biosphere’, scientists are hoping that they can get close to finding life elsewhere in the solar system.

New origins of life are unlikely today, because existing life would gobble up any aggregations of prebiotic molecules before they could edge over the threshold.

However, opportunities for the origin of life may well have existed for long periods on the early Earth.

Some of these origins may have been dead ends, out-competed by other life forms, but others could still be living among us, unnoticed.

“I think if we found a second sample of life on Earth, it would be as big as Darwin’s theory of evolution,” cosmologist and astrobiologist Paul Davies at Arizona State University in Tempe told New Scientist.

“It would answer the most fundamental question we can imagine, which is: are we alone in the universe?” he added.

Skeptics might scoff at the idea that shadow life could pass unrecognized for so long, but Davies and his collaborators have a simple rejoinder: scientists have never looked properly.

Such life would probably take the form of single-celled microbes, so naturalists should not be expected to spot it casually.

The techniques microbiologists use to detect life, like, staining for DNA, sequencing DNA, and culturing microbes in the lab, assume that the target microbes have the normal biochemistry.

“They couldn’t detect an alternative form of microbial life,” said Carol Cleland, a philosopher of science and astrobiologist at the University of Colorado in Boulder.
iven that fewer than 1 per cent of microbes have been cultured and described, there is plenty of room for shadow life to be living right under our noses, according to scientists.

However, the task of searching for shadow life on Earth is much tougher than looking for life on other planets.

“This planet is heavily contaminated with life as we know it,” said Shelley Copley, a biochemist at the University of Colorado.

One promising avenue is to explore extreme environments that are beyond the reach of conventional life, such as ultra-dry deserts, ice sheets, the upper atmosphere or the hottest hydrothermal vents.

According to Davies, more researchers will start looking for shadow life.

Even if they don’t find it, the search could turn up previously unknown branches on the familiar tree of life.

“So, it’s worth doing anyway, even if you’ve convinced yourself that we’re alone in the universe,” he said. (ANI)