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Beijing Genomics Institute, ABI, GATC Biotech, 454, Illumina, Roche, Microchip Biotechnologies, GE Healthcare, New York State Department of Health, Salk Institute

BGI Adds Two ABI SOLiD Sequencers
The Beijing Genomics Institute said last week that it has added two Applied Biosystems SOLiD systems to its collection of DNA sequencers.
The institute said the two SOLiD systems have already been installed and “thoroughly tested” by its researchers. It said that the ABI instrument generated “high quality mate-pair data" with read lengths up to two times 25 base pairs.
BGI intends to use the new instruments for large-scale sequencing projects, such as the Giant Panda Genome project and the International 1000 Genomes Project, and to expand its sequencing services.
Last month, the institute announced that it had added 14 of the high-throughput sequencers that have been introduced to the market over the past couple of years, including 11 Genome Analyzers from Illumina and three Roche Genome Sequencer FLX instruments (see In Sequence, 04/01/08).

GATC Biotech Purchases Second 454 FLX, Illumina GA
GATC Biotech has added a second 454 Genome Sequencer FLX and a second Illumina Genome Analyzer to its lab, the Constance, Germany-based company said in separate announcements recently.
The sequencing services company has purchased an updated version of the Genome Analyzer that enables paired-end reads. GATC said the new instrument would help support increased demand “for projects for which up to 50 bp read length is sufficient,” such as resequencing genomes, microRNA, ChIP sequencing, and other applications.
“The demand for sequencing projects which require a hybrid strategy is increasing,” said Kerstin Stangier, global key account manager for GATC. Stangier explained that adding the second Genome Analyzer to its other systems “allows us to overcome the drawbacks of each system, for example the known homopolymer problem of the [454] pyrosequencing technology.”
The second GS FLX system “enables us to execute very demanding sequencing projects on short notice and handle production peaks much better," Thomas Pohl, CTO of GATC, said in a statement. “For example, we are able to run one instrument with a paired-end application and the other one with single reads.” The company purchased its first GS FLX system in March 2007.
Last summer, GATC also bought an Applied Biosystems SOLiD DNA sequencing system through ABI’s early-access program.
GATC also said that it has been expanding its informatics infrastructure and has been hiring new informaticians and programmers to handle increased amounts of data.

Roche's Molecular Diagnostics, Applied Science Sales Rise in Q1; Sequencing Revenues Double
Roche last week reported that its molecular diagnostics sales increased 4 percent and its applied science sales climbed 19 percent for the first quarter of 2008.
The Swiss pharmaceuticals, diagnostics, and life sciences research giant posted an overall decline in first-quarter sales of 4 percent, due to reduced demand for its influenza drug Tamiflu and the weaker US dollar. It reported revenues of 10.9 billion Swiss francs ($10.9 billion), down from CHF 11.4 million in the comparable period of 2007.
Sales for its diagnostics division grew 3 percent year over year to CHF 2.3 billion from CHF 2.2 billion. Its molecular diagnostic sales rose 4 percent to CHF 270 million, Roche said. The biggest portion of Roche’s molecular diagnostics business, the virology segment, had 4 percent revenue growth, while sales of blood screening products fell 8 percent, “primarily as a result of increased pressure on prices,” said Roche.
The firm expects to receive US clearance of its cobas TaqScreen MPX test, which simultaneously detects HIV and hepatitis B and V in donated blood, in the second quarter of this year.
Roche’s applied science segment reported first-quarter sales growth of 19 percent to CHF 183 million. It noted that its sequencing business doubled revenues compared with the first quarter of 2007 and that it introduced upgrades to the Genome Sequencer FLX and LightCycler 480 instruments during the first quarter.
Sales for tissue diagnostics subsidiary Ventana Medical Systems, which Roche acquired in mid-February for around $3.4 billion, totaled CHF 65 million from the date of acquisition through the end of the first quarter on March 31.
Roche confirmed its guidance for full-year 2008 sales growth in the high single digits.

Microchip Biotechnologies Licenses GE Microfluidics Patents
Microchip Biotechnologies said this week that it has licensed certain patents from General Electric’s GE Healthcare division that cover design and methods for creating integrated fluidic microchip devices.
MBI said the license would “significantly enhance” its intellectual property portfolio supporting development of lab-on-a-chip devices. The Dublin, Calif.-based firm said that it would use the licensed technology to develop and market "sample-to-answer" systems for genomic analyses and molecular diagnostics.
"Microfluidic devices will play a critical role in next-generation instrumentation that delivers fully automated, cost-effective bioassay solutions in the life sciences, applied sciences, and molecular diagnostics,” said Stevan Jovanovich, president and CEO of MBI, in a statement.
Financial terms of the alliance were not disclosed.
Microchip Biotechnologies recently signed up its first early-access user for its first product, an instrument called the Apollo 100 Star that automates DNA sample preparation for Sanger sequencing (See In Sequence, 04/15/08).

New York State Warns Consumer Genomics Services Firms about Offering Tests
The New York State Department of Health has sent warning letters to 23 firms involved in offering consumer genomics services and genetic tests directly to consumers, telling them that they need a permit to offer such tests and services, a department spokesperson told In Sequence’s sister publication GenomeWeb Daily News last week.
Among the firms that were sent letters were Navigenics, 23andMe, Affymetrix, Illumina, and HairDx. Iceland's DeCode Genetics, which offers a consumer genomics service and has been offering the test to New York state residents, has apparently not received a letter from the state.
According to an article on published last week, New York officials were not aware that DeCode was selling its services to New York residents. The department of health spokesperson could not confirm whether DeCode is among the 23 firms that were sent letters.
It is unclear why Illumina and Affymetrix, which are supplying the instrument platforms used to genotype consumers but are not marketing the services themselves, are considered to be violating New York State law. Affymetrix provides lab services for the Navigenics offering via its CLIA-certified laboratory in Sacramento, Calif.
State health officials consider the consumer genomics services to be offering medical tests, which under New York State law would make them subject to medical testing regulations. As such, the firms would need to obtain a permit for offering genetic tests in the state and the tests would have to include a doctor’s order, according to the spokesperson.
She added that the state's attorney general would be notified of firms who continue to offer their services to New York State residents without the proper permit and involvement of a physician.
The consumer genomics firms have countered that the services they offer are meant to be educational, not medical.
DeCode and 23andMe launched their services, which cost around $1,000, around the same time last November. The services use a DNA sample taken from a consumer’s saliva or a cheek swab, and using genotyping tools provide consumers with information about genetic variants associated with risks for common diseases, ancestry, and traits such as hair and eye color.
DeCode CEO Kari Stefansson emphasized at the time of the firm’s launch of the DeCodeMe service that it is not offering a genetic test. “We strongly encourage you not use this to make medical decisions,” he said during a webcast. “If there is something that raises concerns when you look at your result … you can ask a question that will be answered by our experts.” The firm may also refer subscribers to a genetic counselor, he added.
Illumina is providing the genotyping platform and chips for 23andMe’s service, and even though several media outlets have reported that DeCode is using Illumina’s technology for its service as well, DeCode has never publicly verified those reports.
Navigenics, another consumer genomics services firm that is using Affymetrix’s genotyping tools for its offering, officially launched last week. It had previously said that it would offer its services for around $2,500.
In addition to these companies, SeqWright and GATC Biotech have also jumped into the consumer genomics ring, and Knome offers a whole-genome scan for the very high price of roughly $350,000.
The rapid proliferation of these consumer genomics services has brought questions about whether the US Food and Drug Administration will regulate them as genetic tests as well as concerns about keeping data private.
An opinion piece in the New England Journal of Medicine in January called the consumer genomics services “premature attempts at popularizing genetic testing.” The authors of the op-ed includes Muin Khoury, director of the National Office of Public Health Genomics at the US Centers for Disease Control and Prevention; David Hunter, a professor of epidemiology and nutrition at the Brigham and Women’s Hospital at Harvard Medical School; and Jeffrey Drazen, an environmental health professor at Harvard who also serves as NEJM’s Editor-in-Chief.
They argued that the medical field and the public will not be ready to deal with the implications of consumer genomics until more translational medicine connects information from the vast amount of genome-wide association data to personal genomes in meaningful ways.
Against this backdrop, legislation is pending in Congress to protect Americans from genetic discrimination from insurance companies and employers, and some see quick passage of this legislation as crucial as more consumers gain access to their own genetic information.
— By Edward Winnick, originally published by GenomeWeb Daily News

Illumina Sequencing Illuminates Arabidopsis Epigenome
In a paper published in last week’s issue of Cell, researchers from the Salk Institute for Biological Sciences and their collaborators used Illumina sequencing to chart epigenetic modifications — specifically, cytosine methylation — throughout the Arabidopsis thaliana genome. By overlaying this information with messenger RNA and small RNA sequence data, the team was able to delve into the relationships between cytosine methylation, gene expression, and small RNAs.
“There were many small surprises which we found looking through the data,” co-lead author Ryan Lister, a postdoctoral researcher affiliated with the Salk Institute for Biological Studies’ Genomic Analysis Laboratory, told In Sequence’s sister publication GenomeWeb Daily News last week. “The overall message is that it’s now feasible to integrate all these levels of nucleotide information from the cell.”
Cytosine methylation is an important epigenetic DNA modification that alters the way the cell’s transcription machinery binds to specific regions of the genome. Such modifications have been implicated in everything from embryonic development to tumor formation. Enzymes called methyltransferases add methyl to cytosine, while others called demethylases remove them.
For this study, Lister and his colleagues used Illumina’s Genome Analyzer to map the cytosine methylome, transcriptome, and small RNA transcriptome of A. thaliana, a model plant organism with a relatively small and well-defined genome.
To do this, they isolated genomic DNA from A. thaliana floral tissue and treated it with sodium bisulfite, which converts only unmethylated cytosines to uracil and leaves methylated cytosines unchanged. They then analyzed the DNA by high-throughput sequencing.
By incorporating this methylation data with gene expression and smRNA data gleaned from other sequencing experiments, the researchers could look at how the systems interacted. To assess this, Lister said, they relied heavily on a web-based genome browser called AnnoK, developed by collaborators at the University of Western Australia’s ARC Center of Excellence in Plant Energy Biology. The program “allows you to dynamically zoom from megabase data down to an individual nucleotide,” Lister explained.
DNA methylation was more extensive than previously imagined, the authors reported. They found that more than five percent of the cytosines in the nuclear genome of A. thaliana floral bud tissue — some 2,267,447 bases — were methylated. They verified these findings using a ChIP-chip approach, hybridizing a chromatin immunoprecipitation with methylcytosine antibodies to whole-genome tiling arrays.
Though the regions identified by sequencing corresponded to those that fell out of their ChIP-chip analysis, sequencing pulled out nearly twice as many methylated cytosines as the ChIP-chip approach.
“[T]he demonstrated higher sensitivity, increased coverage, and reduced bias of the methylC-sequence approach allows for the discovery of a previously uncharted segment of the Arabidopsis DNA methylome,” the authors wrote.
Interestingly, about a third of the methylated cytosine residues in the genome seem to be associated with smRNAs — a pattern that may provide insight into how the molecules work together to control gene regulation. Specifically, the data suggest smRNAs help target DNA methylation.
“This may be a feedback loop established to reinforce silencing,” Lister explained.
The team also looked at the influence that local sequence had on cytosine methylation and compared epigenetic patterns in mutant A. thaliana strains lacking various methyltransferase or demethylase enzymes. Because these plants have methylation defects — resulting in less or more methylation than usual — they provide insights into the role of methylation within these cells.
For instance, in mutants lacking the methyltransferase met1, the researchers found 11,652 regions in which both DNA methylation and smRNA abundance differed from wild type. In more than 90 percent of these, mutants with lower levels of DNA methylation also had decreased smRNA density.
Altering methylation also changed the expression of hundreds of genes, transposons, and intergenic transcripts.
“Through the simultaneous study of these three interrelated phenomena in wild-type plants and in informative mutant backgrounds, we have helped to illuminate, genome-wide, the scope and sophistication of the interactions that exist between methylation and smRNA, and their ultimate effect on transcriptional regulation,” the authors concluded.

— By Andrea Anderson, originally published by GenomeWeb Daily News