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Invitrogen, Baylor, ABI, Illumina, Helicos, Sanger Institute, Fasteris, ZS Genetics, GINA, SAC Capital Advisors, Sorenson Genomics, NuGen, ACMG, US Justice Dept., International Papaya Genome Consortium

Invitrogen Vows to be ‘Key Player’ in Next-Gen Sequencing Space
Invitrogen said last week that it plans to be a “key player” in next-generation sequencing in the next few years.
During its first-quarter earnings call, Invitrogen Chairman and CEO Greg Lucier said that the company is keen on “capturing a significant opportunity that next-generation sequencing presents to a company like ours.”
He and his colleagues are “excited to play a key role in helping to accelerate the output of the platforms being developed with world-class labeling reagents.”
He added that Invitrogen has “put a dedicated group of R&D and marketing personnel in place to focus solely on the partnerships and product opportunities related to the next-generation sequencing area, using the same model that proved to be extremely successful for us with stem cells. We plan to be a key player in this area in the coming years.”
Lucier did not mention for which sequencing platforms Invitrogen is developing reagents.
In June 2006, Solexa announced an OEM reagent agreement with Invitrogen under which Invitrogen supplied the company with standard reagents for its sample preparation kits (see In Sequence’s sister publication, GenomeWeb Daily News, 6/19/2006).
Invitrogen did not, however, supply proprietary sequencing reagents for Solexa’s system, such as labeled reversible terminator nucleotides or polymerases. Illumina acquired Solexa last year.

Baylor Acquiring Six ABI SOLiD Systems for ‘1,000 Genomes Project’
Baylor College of Medicine’s Human Genome Sequencing Center and Applied Biosystems said last week that Baylor will acquire six ABI SOLiD sequencing systems and use them during the pilot phase of the 1,000 Genomes Project.
The Baylor HGSC will acquire the systems for the first phase of the project, during which scientists there will try to determine the best method for sequencing 1,000 human genomes.
During the pilot stage, the HGSC plans to get significant sequence coverage of 24 human genomes, along with deeper coverage of one human genome. With the systems, the HGSC expects to generate roughly 200 billion bases of sequence in the next four months.
The HGSC also hopes to determine the depth of coverage needed to fully understand sequence variations between individuals — including SNPs, copy number variations, insertions, and deletions.
In a statement, HGSC Director Richard Gibbs noted that his lab chose the SOLiD system for its ability to produce 25- to 50-base-pair reads at very high densities.
“We believe that the SOLiD system will dominate in this arena,” he said. “The production and pooling of data from multiple sources and platforms on the same samples in the 1,000 Genomes Project will help researchers ultimately determine the genetic analysis platform of choice.”
The center selected the SOLiD system for the 1,000 Genomes Project after comparing it with competing short-read platforms for sequencing microbial and mammalian genomes.
“Accuracy is vital, not just for the 1,000 Genomes Project, but for all other applications, too," said Donna Muzny director of operations at the HGSC, in a statement. “The internal error-checking strategy for the SOLiD System makes it superior for the read lengths that are produced,” she said.

Four Genome Centers Own ‘Double Digit’ Number of Illumina Genome Analyzers
Illumina said last week that four genome centers have expanded their installed base of Genome Analyzers into the double-digits.
Most recently, the Beijing Genomics Institute purchased 11 additional Genome Analyzers, bringing its total to 17 machines (see In Sequence 4/1/2008).
Illumina did not mention the other three centers with more than nine Genome Analyzers. As of earlier this year, the Wellcome Trust Sanger Institute owned 27 of the instruments (see In Sequence 2/5/2008).
According to genome center representatives at last week’s Cambridge Healthtech Institute Next-Generation Sequencing conference in San Diego, the Broad Institute currently owns 20 GAs, and Washington University’s Genome Sequencing Center owns 12 of the machines.
“We have worked closely with Illumina to determine ways to dramatically increase our sequencing capacity in order to efficiently and quickly complete several new large sequencing projects,” Xiuqing Zhang, director of the sequencing division of the Beijing Genomics Institute, said in a statement issued by Illumina.
“After rigorously testing this sequencing platform, we opted to purchase the additional Genome Analyzers because of the machine's enhanced level of performance, price, and ease of use,” Zhang said. “Combined with the longer 500bp reads from other platforms, Illumina is the most suitable high throughput sequencing platform for accurate de novo genome sequencing. The collaborative relationship that we established with Illumina this past year also played a significant role in our decision to scale up to 17 Genome Analyzers."

Helicos Reports $11.8M Net Loss in Q1 as Commercialization Proceeds
Helicos BioSciences this week reported an $11.8 million net loss for the first quarter as the company works on additional sales of its Helicos Genetic Analysis System.
The company shipped the first system to Expression Analysis, a genomics services provider, in March (see In Sequence 3/12/2009).
Helicos recorded $113,000 in revenue for the quarter, compared to $92,000 in the first quarter of 2007, stemming from the same NIH grant.
The company’s R&D costs increased 5.3 percent to $5.7 million, from $5.4 million year over year, while its general and administrative expenses nearly doubled to $6.2 million, from $3.3 million.
The firm reported a net loss of $11.8 million, or $.57 per share, compared to $26.5 million, or $17.90 per share, during the first quarter of 2007. Last year’s net loss included an $18.1-million non-cash charge for the conversion feature related to the convertible preferred stock issued in Jan. 2007. These shares converted to common stock in May 2007, when Helicos went public.
Helicos finished the quarter with $37.9 million in cash.

Illumina Paired-End Sequencing Finds Genetic Rearrangements in Cancer Cell Lines
Researchers from the Wellcome Trust Sanger Institute and the University of Cambridge have used paired-end sequencing on Illumina’s Genome Analyzer to identify several types of somatically acquired and germline mutations — including rearrangements, insertions, deletions, and copy number variations — in two lung cancer cell lines.
The paper, published online in Nature Genetics on Sunday, suggests it may be possible to systematically catalogue genome-wide genetic changes in cancerous cells.
“The basic aim is to obtain a genome-wide screen for rearrangements,” Michael Stratton, co-head of the Sanger Institute’s Cancer Genome Project and an author on the paper, told In Sequence’s sister publication GenomeWeb Daily News this week.
For this study, Stratton and his colleagues paired-end sequenced genomic DNA from two lung cancer cell lines —NCI-H2171, a small-cell lung cancer cell line, and NCI-H1770, a neuroendocrine cell lung cancer cell line — using Illumina’s Genome Analyzer.
This involved chopping up the genome into millions of segments — 200 to 500 base pairs in length — and sequencing both ends of these individual inserts. By mapping the ends of each onto a reference genome, the researchers can see what sorts of mutations are present in different parts of the genome.
This sequencing effort, done to two or three times coverage, was specifically aimed at finding genetic rearrangements, Andrew Futreal, co-head of the Cancer Genome Project at the Sanger Institute, told GWDN. Sequencing samples to much greater depth — some 20 times or more — could also provide information about point mutations, he added.
In total, the researchers identified 306 germline structural variants and 103 somatic rearrangements. The germline and somatic, or acquired, mutations seem to result from different biological processes, Stratton noted. Whereas somatic mutations tended to result from double-stranded DNA breaks and acquired tandem duplications, germline variation was more often due to retrotransposons.
And while it’s too early, with just two samples, to find cancer-associated mutation patterns, Futreal and Stratton said this should become possible as they start extending the method to more samples and cancer types. Since the massively parallel paired-end approach is cheaper and more efficient than methods such as end-sequencing BAC libraries, Futreal said, “It’s getting to the point where one can conceive of applying this technique to a larger number of tumor types.”
In the future, he added, the researchers may combine data on short and longer inserts to increase the amount of information they can glean from each tumor sample. Using larger inserts will allow researchers to cover the genome with much less sequence, Stratton said, but makes it more difficult to pinpoint exactly where rearrangements or breakpoints are. “We have to work out the balance of these benefits and costs,” he said.
The Sanger Institute’s Cancer Genome Project is participating in the International Cancer Genome Consortium, which was announced this week (see feature article in this issue).
— By Andrea Anderson, originally published by GenomeWeb Daily News

Fasteris Buys Second Illumina Genome Analyzer
Swiss sequencing service provider Fasteris said last week that it has purchased a second Genome Analyzer from Illumina, which was installed earlier this month.
Fasteris said that it bought a Genome Analyzer II, the latest generation of the high-throughput DNA sequencer, which enables paired-end reads.
The Geneva-based firm purchased its first Genome Analyzer a year ago and said that it would upgrade that system with the new optics of the GA II and with a paired-ends module.
Fasteris CEO Laurent Farinelli also told In Sequence last week that the company has hired more scientists and increased its lab space.

ZS Genetics Enters Genomics X Prize Competition
ZS Genetics said last week that it has joined the Archon X Prize for Genomics competition, a contest sponsored by the X Prize Foundation that will award $10 million to the first research team that can sequence 100 human genomes within ten days for less than $10,000.
ZS Genetics, which is developing a sequencing method based on modified transmission electron microscopy and atomic labeling (see In Sequence 2/20/2007), is the seventh group to join the Archon X Prize competition. Other teams include Visigen Biotechnologies, Roche’s 454 Life Sciences subsidiary, the Foundation for Applied Molecular Evolution, Reveo, base4 innovation, and George Church’s Personal Genome X-team.

Genetic Antidiscrimination Law Passes Senate with Compromises
The US Senate last week unanimously passed the Genetic Information Nondiscrimination Act after senators agreed to compromises that had held up the bill since last summer.
After over a decade of failed attempts to pass the law, which has passed both houses of congress more than once with wide margins, only never in the same session, GINA also is expected to pass in the US House of Representatives as early as this week and be signed into law “in short order,” Kurt Bardella, press secretary for GINA sponsor Olympia Snowe (R – Maine), told In Sequence’s sister publication GenomeWeb Daily News last week.
The bill, which would protect Americans from discrimination based on information from genetic tests, sailed through the House a year ago by a vote of 420 to 3, but never made its way to a Senate vote after it was placed on hold by Senator Tom Coburn (R – Okla.).
Coburn has since raised concerns about the bill focused primarily on the potential for lawsuits and employers’ rights. In March of this year, he and ten other senators signed a letter to the White House listing their complaints, signaling a new threat to GINA’s passage.
“We believe the final draft of GINA should provide clarity to the health insurance industry, maintain the integrity of the underwriting process, and ensure accurate premium assessments,” the senators stated in the letter.
Now, the lawmakers have agreed to a key compromise that would salve Coburn’s concerns by adding language to create a "firewall" between the parts of the bill dealing with insurers and employers, an adjustment Coburn and the White House said was needed to protect them from some lawsuits, a source on Capitol Hill told GWDN last week.
The agreement included other "minor" changes having to do with phrasing, according to the source, who asked to remain anonymous.
Senator Coburn’s office was not immediately available for comment to explain further its stance on the compromises.
As GWDN reported in March, when GINA passed the house as an amendment to another unrelated bill, the Paul Wellstone Mental Health Act, Coburn had other concerns with GINA, and it was not immediately clear how many of these have been agreed upon.
According to Bardella, the Senate will call up the House version of the bill and then insert the changes into the new Senate bill before voting on it and sending it back to the House.
Snowe’s office said it expects the House to pass the bill with unanimous consent and expects President Bush to put his name on it. “We expect the White House will be pleased to sign the bill into law,” Bardella said.
 “Our challenge now is to make sure that doctors and patients are aware of these new protections so that fear of discrimination never again stands in the way of a decision to take a genetic test that could save a life," said Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University.
The pending passage of the bill also was lauded by the Personalized Medicine Coalition, a collection of industry, academic, payor, and other partners who advocate for the advancement of personalized healthcare.
“The guarantees provided by this legislation will encourage millions of Americans to use their genetic information to improve their healthcare, and to help prevent and treat cancer and other diseases,” Edward Abrahams, executive director of the PMC, said in a statement.
Mari Baker, president and CEO of consumer genomics services firm Navigenics, also applauded the Senate’s passage of the bill. “This is fundamental, foundational legislation that’s critical for the long-term ability of using genetic information to improve healthcare in this country,” Baker told GWDN this week.
“With GINA passing, people can now have confidence that this information will not be used to discriminate against them, and this industry can move forward.”

Investment Firm Ups Stake in ABI; Encourages Board to Seek 'Strategic Alternatives'
Investment firm SAC Capital Advisors disclosed in a US Securities and Exchange Commission filing this week that it has increased its stake in Applied Biosystems to 5.1 percent and that it has encouraged ABI’s board of directors to explore strategic alternatives for the firm, including a possible sale.
Stamford, Conn.-based SAC and its affiliated funds have spent roughly $276.2 million over the past two months to acquire 8.6 million shares of ABI common stock, providing the firm with a 5.1 percent stake. ABI had 167,377,025 shares of common stock outstanding as of Feb. 4, according to quarterly report filed with the SEC earlier this year.
SAC noted in this week’s filing that it had sent a letter to ABI’s non-management directors expressing continued support of the firm’s split with sister company Celera and their parent firm Applera. The firms hope to complete the split by the end of June, and Celera recently filed a preliminary prospectus with the SEC as part of that process.
In addition to favoring the split, SAC said that it encouraged the ABI board to take actions that ensure that “excess costs associated with the Applera parent company and the Norwalk, Connecticut headquarters are eliminated instead of being absorbed by” ABI.
SAC also wants current Applera CEO Tony White to cease being an officer or director of ABI, and wants the board to consider a sale of the company. White has yet to say what his role with ABI will be once the split from Celera takes place. ABI President and COO Mark Stevenson was named to that post in December, taking over for White, who had been interim president of ABI for a year following the departure of Cathy Burzik in 2006.
The investment group noted that it has yet to decide whether it will seek to nominate individuals to stand for election to ABI’s board at the firm’s 2008 annual meeting of stockholders.
SAC said that its future actions regarding ABI’s stock will be determined by the board’s actions in response to its suggestions, ABI’s share price, and general economic and industry conditions, among other factors.
As of Dec. 31, 2007, ABI’s largest institutional shareholder was Primecap Management, with a stake of roughly 12.2 percent.
ABI officials declined to comment on SAC’s filing or its recommendations for the board.

Sorenson Relocates Identigene Division
Sorenson Genomics has relocated its Identigene DNA testing division from Houston to Salt Lake City, the firm said this week.
Sorenson recently expanded its genetics lab in Salt Lake City, boosting its DNA testing capability five-fold and increasing its workforce by 25 percent.
Sorenson said that the Houston lab would be closed and “a portion” of Identigene’s workforce would be moved to Salt Lake City.
The move follows Sorenson’s decision last October to merge Identigene with its GeneTree division. At the time, Sorenson said that Identigene would continue to operate in Houston and Salt Lake City.

NuGen Technologies Gets ISO Certification
NuGen Technologies announced last week that it has received ISO 13485:2003 medical device certification for its products.
The San Carlos, Calif.-based firm said that it had received the certification from TUV SUD, an engineering services firm that provides international safety testing and certification services.
NuGen makes rapid, high-throughput nucleic acid amplification and labeling systems used for discovering biomarkers.

ACMG Says Consumer Genetics Needs Informed, Counseled Customers
The American College of Medical Genetics last week issued an advisory statement to the public and the healthcare community about direct-to-consumer genetic tests, saying in a policy paper that consumers need to be counseled on the utility and meaning of these new technologies.
“Just because a genetic test exists, does not mean it is right for everyone or even right for anyone,” ACMG Executive Director Michael Watson said in a statement.
The group advises greater involvement from counselors and doctors with consumers when it comes to making choices about these tests, and for increased oversight and regulation for the nascent consumer genetics industry.
The group proposed five recommendations for health care providers, businesses, regulators, and consumers to consider.
Because genetic testing is “highly technical and complex,” ACMG said, “a knowledgeable professional should be involved in the process of ordering and interpreting a genetic test.” This can help reduce certain risks involved in genetic testing, which include issues of consent, “inappropriate testing, misinterpretation of results, testing that is inaccurate or not clinically valid, lack of follow-up care, misinformation, and other adverse consequences.”
“The consumer should be fully informed regarding what the test can and cannot say about his or her health,” the group contended. Because interpretation of results is “highly nuanced … such information needs to be communicated to the consumer in the appropriate context and in an understandable fashion,” ACMG advised.
The group also asserted that the “scientific evidence on which a test is based should be clearly stated.”
In addition, ACMG said that labs involved in offering these genetic testing services “must be accredited by CLIA, the state and/or other applicable accrediting agencies,” and this accreditation should be shared with the consumer along with test results.
Finally, privacy concerns also must be addressed, the group said. Consumers should be informed about what will happen to their results, who will have access to them, and how they may find out information about privacy breaches that may occur, ACMG said. Other privacy matters that should be discussed with consumers include employment and insurance discrimination issues and the potential impact the results of tests may have on family members.
“The potential benefits to mankind are tremendous but there are a great many questions still to be answered and more research to be done to better understand how genetics affects many conditions,” ACMG President Joe Leigh Simpson said in a statement.

US Justice Dept. Aims to Expand Scope of DNA Sample Collection
The US is planning to expand the collection of DNA samples to include all people who are arrested or detained under federal authority, as well as any non-US citizens who are detained, according to a rule proposed by the Department of Justice.
In an effort to advance the ability to use DNA information to solve a broader array and volume of crimes, the Justice Department is planning to implement amendments that would expand federal DNA collection policies under the primary law covering DNA analyses in the Federal Bureau of Investigation’s Combined DNA Index System.
All 50 states already allow collection and analysis of DNA samples from convicted state offenders, but until recently, the collection of DNA samples by federal authorities was limited.
The DNA Analysis Backlog Elimination Act of 2000 initially authorized DNA collection only from persons convicted of certain “qualifying” federal, military, and District of Columbia offenses. This authority was later expanded by several subsequent acts, including the DNA Fingerprint Act of 2005 and the Adam Walsh Child Protection Safety Act of 2006.
The proposed rule would implement aspects of these two acts under the DNA Analysis Backlog Elimination Act of 2000, which would direct US agencies that arrest or detain individuals “to collect DNA samples from individuals who are arrested, facing charges, or convicted, and from non-United States persons who are detained under the authority of the United States … for purposes of analysis and entry into the Combined DNA Index System.”
The rule would limit the collection of samples to “individuals from whom an agency collects fingerprints,” and would give the attorney general the latitude to approve certain exceptions or limitations about who may obtain samples.
The DOJ published the DNA Sample Collection rule in the Federal Register last week and is currently taking public comments. The rule has been called an invasion of privacy and an unwelcome expansion of police powers by the American Civil Liberties Union.
The new rules may reflect an “eagerness to collect a growing amount of private information about innocent people,” ACLU legislative counsel Jesselyn McCurdy told In Sequence’s sister publication GenomeWeb Daily News in an e-mail. “This completely undermines the presumption of innocence in the American criminal justice system,” said McCurdy, who believes this kind of DNA collection “is likely to increase racial profiling and discrimination against people of color.”
McCurdy also believes that the law, or the application of the law, may prove to be unconstitutional.
“What Congress and the DOJ have done is once again skirt around the edges of the Fourth Amendment search and seizure requirements,” she told GWDN.
The DNA fingerprinting proposal is similar to an ongoing program in the UK, where there is a DNA database of samples from criminals, suspects, and crime scenes, which began in the mid-1990s.
While privacy issues have been raised in the UK over the law, there now is some discussion that the entire population of the UK should be sampled and stored in a massive UK DNA database. This sweeping project also would take DNA samples from any visitor to the UK who plans to stay in the country longer than one week.
Senator Jon Kyl (R – Ariz.), who is listed as a co-author of the 2006 US law, believes this expanded power will enable the government to solve many crimes that are otherwise difficult to prosecute and to prevent crimes not yet committed.
“The regulations will save lives, prevent crimes and bring justice for victims and their families,” Kyl said in a statement last week.
Kyl also does not see the worries about privacy as warranted. “Most crime labs don’t even have the equipment to extract medically sensitive information from DNA samples, and it would be a federal offense for any lab employee to misuse a DNA sample in this way,” he said.
The proposed rule does not include information on how long federal authorities will retain DNA samples or what would happen to these samples in cases where detainees are later found innocent or if charges against them are dropped.
While the DOJ lays out general rules for how the policy is to be implemented and how samples are to be collected and handled, it is left up to the individuals who have been arrested or detained to clean their records if they are not convicted of a crime.
In order to have DNA profiles expunged from the database, it is incumbent on individuals to obtain proof that their underlying arrest did not result in a conviction, or that the underlying conviction was overturned, and then to submit that documentation to the appropriate agency, the DOJ said.
The DOJ will hold an open a comment period for 30 days on the new regulations.
— By Matt Jones, originally published by GenomeWeb Daily News

Researchers Sequence Transgenic Papaya Genome
An international team of researchers has sequenced the papaya genome.
The sequence — generated from a transgenic papaya — provides insights into the genetic basis of the plant’s resistance to some microbial pests and into the properties that separate papaya from other flowering plants. An analysis of the genome was published in Nature last week. In addition, researchers say, the detailed genetic information may help alleviate the fears of those opposed to transgenic papaya plants.
After pineapple, papaya is Hawaii’s second largest fruit crop. In the 1990’s, though, a devastating virus called the papaya ringspot virus slashed papaya harvests in that state. Scientists at the US Department of Agriculture, the University of Hawaii, Cornell University, and elsewhere created a genetically modified papaya — resistant to the papaya ringspot virus — by introducing some of the pathogen’s genetic information into the papaya.
These genetically modified papaya plants were introduced as crop plants in Hawaii in the mid-1990s and fruit from these plants is currently marketed in the mainland US and Canada. Nevertheless, some countries have resisted the genetically modified papaya citing concerns over the effect the genetic alterations might have.
In an effort to get to the bottom of papaya genetics and the effect of transgenic modifications, the International Papaya Genome Consortium sequenced a red-fleshed transgenic papaya variety called SunUp. The collaboration involved researchers at 22 research institutions in the US and China and was led by Maqsudal Alam, the director of the University of Hawaii’s Advanced Studies in Genomics Proteomics and Bioinformatics program.
The team sequenced 75 percent of the papaya genome and about 90 percent of its genetically active euchromatin sequence at three times coverage using 2.8 million whole-genome shotgun sequencing reads. When they excluded low-quality reads and sequence that came from organelles, the team was left with 1.6 million high-quality reads, which were assembled into contigs and annotated using the TIGR Eukaryotic Annotation Pipeline. Alam and his colleagues then compared papaya sequences with those of other plants such as Arabidopsis, poplar, and grape.
Based on their predictions, the 372 megabase papaya genome contains roughly 23,000 to 25,000 genes. Although it is roughly three times the size of the Arabidopsis genome, the papaya genome has the fewest functional genes of any flowering plant sequenced to date. This may be because — unlike other flowering plants — the papaya genome doesn’t seem to have experienced a recent duplication.
Even so, papaya has genetic expansions related to specific functions. For instance, compared to Arabidopsis, papaya has more starch-related genes and genes coding for volatile compounds that attract insects and other pollinators. And, consistent with its tree-like characteristics, the papaya genome has more genes related to increased cell expansion and the synthesis of the woody polymer lignin.
Because SunUp is a transgenic papaya variety, the authors noted, sequencing its genome also provides clues about how transgenic techniques affect genome structure and function. Using Southern blot analysis, they identified three transgenic insertions in the SunUp nuclear genome. These were closely associated with chloroplast DNA sequences and did not appear to disrupt nuclear genes.
 “Arguably, the sequencing of the genome of SunUp papaya makes it the best-characterized commercial transgenic crop,” the authors wrote. “Because papaya ringspot virus is widespread in nearly all papaya-growing regions, SunUp could serve as a transgenic germplasm source that could be used to breed suitable cultivars resistant to the virus in various parts of the world. The characterization of the precise transgenic modifications in SunUp papaya should also serve to lower regulatory barriers currently in place in some countries.”
The transgenic papaya draft genome sequence has been submitted to GenBank.

The Scan

Genome Sequences Reveal Range Mutations in Induced Pluripotent Stem Cells

Researchers in Nature Genetics detect somatic mutation variation across iPSCs generated from blood or skin fibroblast cell sources, along with selection for BCOR gene mutations.

Researchers Reprogram Plant Roots With Synthetic Genetic Circuit Strategy

Root gene expression was altered with the help of genetic circuits built around a series of synthetic transcriptional regulators in the Nicotiana benthamiana plant in a Science paper.

Infectious Disease Tracking Study Compares Genome Sequencing Approaches

Researchers in BMC Genomics see advantages for capture-based Illumina sequencing and amplicon-based sequencing on the Nanopore instrument, depending on the situation or samples available.

LINE-1 Linked to Premature Aging Conditions

Researchers report in Science Translational Medicine that the accumulation of LINE-1 RNA contributes to premature aging conditions and that symptoms can be improved by targeting them.