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Short Reads: Jan 27, 2009


Jury Sides with Life Tech in Second Phase of IP Suit with Illumina

Life Technologies said this week that a jury in the US District Court for the Northern District of California has decided in its favor in the second phase of an ongoing patent-infringement suit with Illumina.

After a seven-day trial, the jury unanimously decided that Life Tech's Applied Biosystems SOLiD sequencing technology does not infringe a patent at the heart of the dispute, the company said.

Illumina had alleged that the SOLiD system infringed US Patent Nos. 5,969,119; 5,750,341; and 6,306,597. The court had already ruled in August that ABI does not infringe the asserted claims of the '341 and '597 patents. The jury decision announced this week clears ABI of infringing the '119 patent.

Kip Miller, president of the genetic systems division at Life, said in a statement that the company is "pleased" with the decision, which "validate[s] our belief that the SOLiD sequencing system is unique in its design."

Earlier this month, Illumina won the first phase of the trial, in which the jury found that Illumina owns the patents that are the subject of the suit.

An Illumina spokesperson was not immediately available for comment

Helicos BioSciences to Present C. Elegans Sequencing Project at AGBT

Helicos BioSciences is sequencing the genome of C. elegans on its Helicos Genetic Analysis System and plans to provide results from the project next week at the Advances in Genome Biology and Technology meeting in Marco Island, Fla., In Sequence has learned.

Last spring, the company published a study in Science in which it resequenced the genome of the M13 virus, the first organism analyzed with a single-molecule sequencing technology (see In Sequence 4/8/2008).

At a conference last fall, Helicos researchers presented results from bacterial genome-sequencing projects and yeast transcriptome-analysis projects (see In Sequence 9/30/2008).

According to a Helicos spokesperson, the C. elegans study was an internal project. Details will be provided by the company’s chief technology officer and senior vice president Bill Efcavitch at the AGBT meeting on Thursday.

Researchers from WashU Genome Center to Present Comparison of Short-Read Aligners at AGBT

Researchers from the Genome Center at Washington University in St. Louis plan to present results from a comparison of at least 10 short read aligners during a poster session at the Advances in Genome Biology and Technology meeting in Marco Island, Fla., next week.

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According to Dan Koboldt, one of the scientists involved in the project, the alignment tools “were systematically evaluated on both simulated and real data sets.”

Simulated datasets were derived from a reference genome but “trained” on data from actual runs on the Illumina Genome Analyzer. The researchers introduced and tracked systematic mutations, such as SNPs and indels, to assess their effect on read alignment.

For each aligner, they calculated the CPU time, memory usage, number of reads placed, number of reads uniquely placed, and number of reads correctly placed.

They also applied the aligners to real whole-genome Illumina GA data that were generated as part of the 1,000 Genomes Project.

According to a posting on Koboldt’s blog, MassGenomics, the short-read aligner comparison includes Maq, Novoalign, Bowtie, cross_match, RMAP, and SOAP.

NCGR Obtains 20.5 Gigabases from Illumina GA Run

The National Center for Genome Resources said last week that it has produced 20.5 gigabases of high-quality DNA data from a run on an Illumina Genome Analyzer II.

The Santa Fe, NM-based institute generated the data, which passed certain quality metrics, as part of a project that seeks to identify genetic risk factors for multiple sclerosis. NCGR said its researchers created approximately 13 million paired reads of two times 106 bases in each of seven flow cell channels. The average quality score of the sequence was greater than 25, and the average error rate was 0.91 percent.

The project is a collaboration between NCGR; the department of neurology at the University of California, San Francisco; and Illumina. It is funded by Small Ventures USA, the Brass Family Foundation, and the Nancy Davis Foundation.

In a second project, designed to sequence the genome of an individual from South Korea, NCGR generated 18.8 gigbases of sequence data in a single run using a long-insert 4-kilobase paired-end library. This project is funded by, and conducted in collaboration with Macrogen and the ILCHUN Genomic Medicine Institute at Seoul National University.

The NCGR Genome Center is a collaboration with the New Mexico Institute of Mining and Technology. The center currently houses six Illumina Genome Analyzer IIs and provides large-scale sequencing and analysis services to collaborators throughout the world.

Sequencing projects conducted at NCGR include a study to identify genes linked to schizophrenia, a cotton genome-sequencing project, and several legume crop-sequencing projects.

1000 Genomes Project Releases First Set of SNP Calls

The 1000 Genomes Project last month released the first set of SNP calls for four individuals sequenced at high coverage as part of a pilot project.

According to the project’s website, the preliminary release is designed to provide data to the community and to test the data release systems, including the 1000 Genomes browser.

The SNPs represent a preliminary analysis of a portion of the data collected since the 1000 Genomes Project began in early 2008. The project expects to make additional updates of the site and the 1000 Genomes browser throughout January. It also plans to release additional raw project data “as soon as

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possible” through the National Center for Biotechnology Information and the European Bioinformatics Institute.

Users in the Americas can download the data from NCBI via an ftp server or via the Aspera high-speed data-transfer client.

Other users can download the data from the EBI, which plans to implement an Aspera client in the near future.

Raw data for a portion of the 1000 Genomes Project pilot phase is already available through the Short Read Archive at the NCBI and the European Read Archive at the EBI. These archives will be making the complete project data available “as soon as possible.”

The 1000 Genomes Project plans to release quarterly summary data beginning this month. Summary data releases will include SNPs and CNV analyses for the six high-coverage individuals and all of the low coverage individuals.

Transcriptome Sequencing Uncovers Breast Cancer Rearrangements

In a paper scheduled to appear online this week in PNAS, an international research team has published a proof-of-principle study using high-throughput transcriptome sequencing to pick up genomic rearrangements in a breast cancer cell line.

Researchers from the J. Craig Venter Institute, three branches of the Ludwig Institute for Cancer Research, and New York's Memorial Sloan-Kettering Cancer Center used Roche 454 transcriptome sequencing to look for translocations in a highly rearranged breast cancer cell line. In the process, they identified seven new genomic rearrangements — resulting in five gene truncations and two chimeric proteins — that they believe affect at least nine genes.

Senior author Robert Strausberg, deputy director of genomic medicine and group leader at JCVI, said he credits high-throughput sequencing for providing researchers with access to new types of information in the transcriptome. "It's a dream come true to be able to look at this many transcripts in a cell," he told In Sequence’s sister publication GenomeWeb Daily News.

Strausberg and his team interrogated the transcriptome for clues about translocation events in the genome. In an effort to detect the active gene products of genomic rearrangements, they used 454 sequencing to assess the transcriptome of the highly rearranged breast cancer cell line HCC1954.

The researchers pulled out 496 potential chimeric transcripts containing information from at least two different genomic locations. Roughly half of these represented rearrangements within the same chromosome, while the other half involving different chromosomes.

The team then experimentally validated 13 chimeric cDNA. Most of the changes they detected were also present in a control line derived from the same individual's blood cells. That prompted the researchers to use long-range PCR, Sanger end-sequencing, and fluorescence in situ hybridization to distinguish between trans-splicing events and genuine genomic rearrangements.

While some of the rearrangements they detected overlapped with known changes in the cell line, others were new, lead author Qi Zhao, a human genomic scientist at JCVI, told GWDN. For instance, the researchers identified four inter-chromosomal translocations and one intra-chromosomal rearrangement in their initial experiments.

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Next, the team went back to look for chimeric transcripts that mapped to more than one spot in the genome. In the process, they identified and verified two more inter-chromosomal rearrangements.

Together, the seven rearrangements identified in the study are thought to affect at least nine different genes. Five of the rearrangements produced transcripts coding for truncated proteins, including proteins with known oncogenic functions.

For instance, the researchers detected a truncation in MRE11A, a gene coding for a protein involved in double-strand break repair that has been detected in several breast cancers, as well as NSD1, a gene coding a potential transcription regulator that's sometimes fused in acute myeloid leukemia.

Beyond this proof-of principle study, Strausberg said the ultimate goal is to understand cancer at a clinical level. He and his co-authors emphasized the need to compile and integrate different types of data, including genomic rearrangements and alternative splicing events, to improve the chances to translating research into better outcomes.

"Databases that provide the ability to compare and contrast these changes across a broad range of cancer will be essential for identifying features that might be shared across cancers, thereby affording opportunities to apply new intervention approaches effectively to all cancers for which patient outcomes might be improved," the authors concluded.

By Andrea Anderson; originally published on GenomeWeb Daily News

Artemis Licenses Non-Invasive, Prenatal Dx Technology from Stanford

Artemis Health said this week that it has licensed co-exclusive worldwide rights from Stanford University to develop cell-free fetal DNA prenatal diagnostic tests based on research carried out in the lab of Stephen Quake.

Menlo Park, Calif.-based Artemis said that the licensing deal will expand its clinical and research program and allow it to develop a non-invasive prenatal blood test that predicts chromosomal and genetic disorders. The privately held firm, which was formed in 2002, has a parallel development program focused on the isolation of intact fetal cells from maternal blood for advanced genetic analysis.

Artemis President and CEO Lissa Goldenstein told GenomeWeb Daily News this week that the firm is developing tests based on both methodologies. "We were originally focused on the intact fetal cell, and we continue making progress along that path," she said. "But the Quake opportunity allows us to really broaden our research to include both the intact fetal cell and cell-free fetal DNA."

The license from Stanford covers the use of digital PCR and shotgun sequencing to analyze cell-free fetal DNA from maternal blood, particularly for the diagnosis of fetal genetic disorders, such as Down syndrome, Edwards syndrome, and Patau syndrome. Artemis also noted that it has extended its exclusive consulting relationship with Quake.

Goldenstein said that Artemis plans to initially launch products as laboratory developed tests while in parallel working toward Food and Drug Administration clearance. "We feel very confident that we'll have some study data within the next 12 months" that will prove the test is effective, and a commercial launch will follow, she said.

Quake's approach was detailed in a paper appearing in PNAS in early October. The researchers used digital PCR and shotgun sequencing to sequence all of the cell-free DNA in the mother's blood plasma.

Though Quake's team used Illumina's Genome Analyzer to sequence a mixture of maternal and fetal DNA fragments, Artemis does not have a preference for which technology is used for the back end of the testing process.

The firm was initially founded based on microfluidics technology that was developed at Massachusetts General Hospital and Harvard University. It uses the technology to separate out the maternal cells without hurting the fetal cells, explained Goldenstein.
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"However, other than that, we are technology agnostic," she said. "Our focus is on using the best technology on the market today and in the future to get these tests to women and their physicians. So, we are not locked into any hardware platform."

Quake has applied for a patent on the methodology outlined in the paper and has also licensed the IP to Fluidigm. In addition, he is a co-founder of Fluidigm and the chair of that company's scientific advisory board.

A similar method of prenatal screening has been employed by Sequenom in collaboration with researchers from the Chinese University of Hong Kong, which demonstrated that they could use massively parallel DNA sequencing to detect Down syndrome from cell-free fetal DNA in pregnant women’s blood. Their findings were published in PNAS in early December.

Sequenom is currently conducting studies on its SEQureDx test, which uses its mass spectrometry platform to diagnose trisomy 21 from fetal RNA in maternal blood. The firm hopes to commercialize that test this year.

Asked whether there are any concerns about a potential intellectual property dispute, Goldenstein said, "We've carefully reviewed the IP around all of our approaches and technology platforms that would be needed to take it to market, and we are confident that have all of the IP protection we would need to be able to take this to market."

Alloy Ventures, Mohr Davidow Ventures, and Sutter Hill Ventures are among Artemis' venture capital backers, and Goldenstein said the firm doesn't see financing as a limitation to getting the tests to market. She also said the firm may partner with some of the larger lab companies, regional labs, and hospital labs to cast a wide distribution net once it receives FDA clearance.

By Edward Winnick; originally published on GenomeWeb Daily News

Invitrogen, ABI Merger Valued at $5.1 Billion

The November merger of Invitrogen and Applied Biosystems to form Life Technologies has been valued at $5.1 billion, down from the initial estimate of $6.7 billion.

Life Technologies disclosed in a filing with the US Securities and Exchange Commission last week that the value of Life Technologies shares issued in the transaction was around $1.8 billion, while the cash portion of the deal was roughly $3.2 billion. ABI shareholders received a total of approximately 80.8 million of the combined company's shares.

When the merger agreement was announced in June, the firms valued the deal at $6.7 billion. However, that was before the stock market tumbled in the fall, cutting the valuations of firms across the board.

NCRR Gives USC $22.2M for National Bioinformatics Center

The University of Southern California has landed a $22.2 million grant from the National Institutes of Health to become a central coordinating point for a national bioinformatics and biomedical data collection and integration project, according to NIH's Biomedical Informatics Research Network.

The National Center for Research Resources funding, which will span five years, will support the establishment of the Biomedical Informatics Research Network Coordinating Center at USC, which the university said will make it "a central clearing house" for information from the BIRN.

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BIRN, which was launched in 2001, was formed to foster large-scale collaborations in biomedical science by using new information technologies, and it aims to implement and distribute shared resources that will be usable to all biomedical researchers involved in disease diagnosis and treatment studies.

The need for a center for biomedical data springs from the "overwhelming quantity of data that geneticists and others produce," which can keep medical researchers from connecting with new discoveries and therapies.

The center will be led by USC Professor Carl Kesselman at the Viterbi School of Engineering Epstein Department of Industrial and Systems Engineering and the USC Information Sciences Institute. "Without a sophisticated bioinformatics capability — which only top engineers can provide — we cannot hope to translate the basic science into drugs and treatments that will improve the quality of life," Kesselman said in a statement.

He also said that the BIRNCC program "can accelerate the rate of discoveries for many areas of biomedical research."

The BIRN program has data centers at universities across the country that are involved in data collection, storage and management, quality assurance and analysis, and data sharing, integration, and discovery.

Fluidigm, ABI Agree to Drop Legal Skirmish

Fluidigm and Life Technologies' Applied Biosystems business have ended legal actions against each other related to Fluidigm's BioMark System, a Fluidigm spokesperson told In Sequence’s sister publication GenomeWeb Daily News last week.

The firms agreed this month to dismiss the case, which Fluidigm filed against ABI in June 2008, according to court documents. Howard High, the Fluidigm spokesman, told GWDN that the agreement does not involve any exchange of money or licensing of products.

In its suit, Fluidigm sought a declaration from the US District Court for the Southern District of New York that its technology did not infringe ABI's patent, US No. 6,814,934. The patent is entitled “Instrument for Monitoring Nucleic Acid Amplification” and was issued to ABI in November 2004.

The suit was in response to a letter it had received from ABI demanding that the firm “immediately cease and desist from the manufacture, importation, use, sale, and offer of sale of [Fluidigm’s] BioMark System for Genetic Analysis” in jurisdictions in which ABI’s patent is valid.

"As we got into the prep for the trial activity we found that the two companies had some mutually interesting product opportunities, and exploring those opportunities was difficult with litigation pending between the two of us," said High. "So, we basically decided to end it."

However, he said the firms have reserved the right to pursue legal action in the future under the agreement.

Fluidigm's BioMark System was launched in 2006. Last year, the firm rolled out a new version of the system, which is configured to run 96 samples against 96 primer-probe sets and can be used to conduct both gene expression and genotyping experiments.

Li-Cor Offers to Help Colleges Buy Its DNA Analysis Systems

Li-Cor Biosciences has pledged to give $1.75 million in matching funds to help colleges purchase its DNA analysis systems for use by undergraduate students, the Lincoln, Neb.-based company said last week.

The Genomics Education Matching Funds program is aimed at helping qualifying colleges pay for the company’s 4300 DNA Analysis System by providing up to 60 percent of the funding.

Li-Cor said that its DNA analysis systems are used in academic labs for sequencing, microsatellite analysis, SNP discovery, and reverse genetics research.