Saturday | 10 January, 2009
Australian Biotechnology News
Genome meeting hears of 'ecogenomics'
John Russell (Bio IT World) 12/10/2004 14:15:55

New chips, new terminology -- 'ecogenomics' -- and the latest installment of J Craig Venter's travelogue of discovery highlighted the opening day of the 16th International Genome Sequencing and Analysis Conference, being held in Washington, DC, last week.

Clare Fraser, president of GSAC organiser the Institute for Genomic Research, reviewed research on the anthrax microbe, Bacillus anthracis, including a genomic comparison with Bacillus cereus. An outgrowth of that research is a collaboration with Affymetrix to develop a chip to genotype strains of Bacillus. Fraser said the chip, which has more than 500,000 probes, can identify 3400 Bacillus single-nucleotide polymorphisms (SNPs). Early work has demonstrated 90 percent accuracy at calling SNPs, necessitating new hybridisation protocols and software development.

"We'd like to get the [accuracy] numbers up," Fraser said. "We'll be able to look for strain-specific information." In developing SNP data, Fraser's team looked at conserved sequences from 1200 different isolates and is now analysing the data.

Another ambitious chip development was described by Joseph DeRisi of UCSF. He reported progress in developing a "pathogen discovery chip" that will include genomic markers for "every virus ever discovered for which sequence information is known." He is including information on family, genus, and species attributes.

"We select the most highly conserved DNA and make 70-mer oligos. No single oligo will give you the identity. In some cases it may take a 100 oligos, and the software for deconvoluting the oligo set is complex," said DeRisi. His first chip had 11,000 markers and the latest version has 22,000 markers, which DeRisi said represents information on all of the virus genomes stored in GenBank as of June.

DeRisi, a former student with Stanford's microarray pioneer Pat Brown, reported that his team's early efforts to use the chip to identify rhinovirus have been extremely successful. A bug's genome

Much of the day was occupied with descriptions of work to capture and characterise microbial genomes. Delivering the opening talk, Ed Wilson, emeritus professor of Harvard University, made an impassioned plea for support of All Species Program to identify and capture information about all species on Earth in 25 years.

"One challenge is simply getting a good definition of species. The prevailing definition is a 'closed gene pool' but that's not realistic for prokaryotes and organisms with asexual reproduction and lateral gene transfer," said Wilson. "The species concept for the microbial world will emerge, but a working definition is needed now."

Craig Venter, freshly back from Australia, reported his progress on sampling the oceans of the world for microbes. Following a 'proof-of-concept' study of the Sargasso Sea, Venter set sail in earnest, beginning at Halifax, Nova Scotia, and heading southward with stops along the way including the Galapagos Islands, retracing much of Charles Darwin's historic voyage on the Beagle. Venter reported finding five million genes and 7000 new species on the journey so far, and indicated the Sorcerer II will head next into the Indian Ocean.

Venter said he'd started to do some clustering analysis of genes by geography. This concept was echoed in presentation by Eddy Rubin, director of the Joint Genome Institute, Lawrence Berkley National Laboratory, who has been doing extensive sampling of soil microbes and sequencing their genomes. Much of that work is aimed at helping the Department of Energy develop methods to clean up Superfund sites.

Rubin coined the term "environmental genomic tagging" (EGT) for clustering genes by the geography of their locations. "EGT fingerprints may serve as diagnostic for the environment in terms of its health and its agricultural capacity, for example." Venter dubbed those efforts as "ecogenomics".

Genomic medicine progress

The future of genomic medicine seemed much closer at GSAC -- as speaker after speaker discussed ongoing projects and trumpeted the value of the new 'omics' and new tools. Anna Barker, deputy director for strategic science initiatives at the National Cancer Institute, set the stage, telling delegates she was now confident personalised medicine would become reality in the not terribly distant future.

Perhaps the most comprehensive evidence that this might indeed be true came from Dahlia Cohen, global head of functional genomics, Novartis Institute for Biomedical Research. "Our view of functional genomics is complex. It's an integrative two-tier approach. Tier one is disease-specific. Tier two is technology and tools," said Cohen, who then provided snapshots of disease programs using a wide variety of technologies, including expression arrays, siRNA knockdown vectors, cell-based pathway screens, and proteomics mapping. She reviewed Novartis AG's work with these technologies in programs on neuropathic pain management, Alzheimer's research, and influenza.

Victor Velculescu, professor of oncology at Johns Hopkins, reviewed work characterising colorectal and brain cancer, and Joseph Nevins of Duke University Medical Centre showed how combining multiple microarray experiments with clinical data could be used to effectively model breast cancer outcomes and suggest therapeutic strategies.

What's more, said Brad Margus, CEO of SNP specialist Perlegen Sciences, "Pharmaceutical companies are making a more consistent effort to collect tissues for DNA extraction." This had been a stumbling block. Venter's trials

Craig Venter's round-the-world voyage to sample the ocean's genomes was briefly interrupted when his research yacht, Sorcerer II, was impounded in the Marquesas islands in Polynesia. But no unauthorised sampling was conducted, according to a Venter spokesman.

"While we sorted out the MOU/permit issues, we never sampled until after these issues were settled. We did not sample illegally anywhere," said Heather Kowalski, vice-president of policy and planning at the Centre for the Advancement of Genomics (one of three Venter organisations just merged into the J Craig Venter Institute.)

Obtaining required permits to sample local waters has been an ongoing struggle for expedition organisers. Indeed, the Sorcerer II is now in Australia and the details of sampling authorisation there had not been finalised as of last Wednesday, according to Robert Strausberg, vice-president of research at the Institute for Genomic Research and charged with overseeing the expedition's permitting process.

Strausberg said one Australian official told him, "I think you now have every permit we have." Strausberg didn't seem worried about obtaining final permission, but emphasised the time-consuming nature of the process as more countries understandably worry about potentially lost commercial value in the sequences discovered in their territorial waters. The intellectual property rights around new useful genes and their products might prove huge.

Venter has promised to put all of the sequences identified in the public domain. Following sampling in Australia, the Sorcerer II will head into the Indian Ocean.

There has even been talk of sampling in Antarctica, said Strausberg -- an obviously difficult challenge with regard to obtaining authorisation since so many countries claim pieces of it. Quipped Strausberg, "If there aren't laws when we arrive [at a sampling site], there are by the time we leave."

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