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Short Reads: Dec 9, 2008

Helicos to Lay Off 30 Percent of Workforce to Cut Costs; Retracts Order Guidance
Helicos BioSciences plans to reduce its workforce by approximately 30 percent in a bid to cut costs, the company disclosed in a filing with the US Securities and Exchange Commission last week.
In the filing, Helicos said that the layoffs, which will occur in the current quarter, are intended to reduce its operating costs and “direct its resources to continue advancing towards the company’s near term goals.”
The company expects to incur approximately $450,000 in severance and termination costs in the fourth quarter of 2008 as a result of the restructuring. A Helicos spokeswoman declined to reveal how many employees the company will have following the reduction.
Helicos said that it has also decided to stop providing forward-looking guidance for its financial results and system orders. As a result, the company said in the filing, “we retract all previous guidance, including with respect to order guidance for 2008 through the second quarter of 2009.”
In September, Helicos anticipated a total of between five and 10 orders for its HeliScope instrument by the end of this year and a total of 15 to 30 orders by mid-2009, but the company warned in its third-quarter earnings call last month that orders would likely be at the low end of that guidance (see In Sequence 11/11/2008).
Helicos said last week that it may provide forward-looking guidance again “when there is more visibility to the market uptake rate for our products.”
As of Sept. 30, Helicos had $12.3 million in unrestricted cash, $8.9 million in working capital, and $10.4 million in restricted cash.

Broad to be Early Access Partner for RainDance Sequence Enrichment Platform

RainDance Technologies said this week that the Broad Institute will become an early access partner for the firm’s RDT 1000 instrument and sequence enrichment application.

The Broad will have access to the RDT 1000 microfluidics-based instrument, consumables kits, and training for sequence enrichment, said RainDance. In addition to applying it in its genomic research initiatives, the Broad will investigate using the RDT 1000 for experiments related to the human microbiome.

The RDT 1000 generates picoliter-volume PCR reactions at a rate of 10 million reactions per hour, and the sequence enrichment application uses a library of PCR primers in droplets to amplify hundreds to thousands of genomic loci in a single tube, the company said.

“The program provides an opportunity for some of the world’s leading scientists in genomic research to become experienced with our technology months prior to its commercial launch,” said Chris McNary, president and CEO of RainDance, in a statement.

RainDance previously said that it intends to commercially launch the system during the first quarter of 2009.

The Broad is the third early access partner announced by RainDance, following the Genome Center at the Washington University School of Medicine in St. Louis last month and the J. Craig Venter Institute in October.


European Consortium Launches $15M Project to Develop New DNA Analysis Tools
A consortium of 16 European academic and commercial research groups announced a four-year program last week that aims to develop new DNA sequencing technologies and other methods for analyzing nucleic acids (see two feature articles in this issue here and here).
The Revolutionary Approaches and Devices for Nucleic Acid Analysis, or READNA, consortium involves researchers from 10 academic institutions. Also participating are six companies: Oxford Nanopore Technologies, Applied Biosystems, Febit, Olink Bioscience, and Philips Research.
The effort is receiving €12 million ($15 million) in funding from the European Union’s Seventh Framework Programme for Research and Technological Development through May 2012.
The consortium is focused on developing fast and cost-effective sequencing methods, improving existing sequencing technology, developing high-resolution techniques for assessing genome-wide methylation, assessing rare mutations and copy number variations, and analyzing RNA and DNA using a single device.
“The project is designed to further medical science and ultimately to drive improved health outcomes,” project coordinator Ivo Gut, director of the Centre National de Genotypage, said in a statement. “We will focus on the development of new nucleic acid technologies, and also improve existing ones.”

Sequenom, Stanford Stake IP Claims for Sequencing-Based Prenatal Test Methods;
Stanford to Compare Helicos and Illumina Platforms for Its Own Test
A recent paper by researchers at Sequenom and the Chinese University of Hong Kong is confirming the feasibility of using high-throughput sequencing of fetal and maternal DNA in a mother’s blood as part of a non-invasive prenatal test for Down syndrome. But with it come new questions over intellectual property related to the test.
In a paper appearing online last week PNAS, Chinese University of Hong Kong researcher Dennis Lo led a team of investigators who demonstrated that they could use massively parallel DNA sequencing, using Illumina’s Genome Analyzer, to detect Down syndrome from cell-free fetal DNA in pregnant women’s blood. The researchers pinpointed more than a dozen Down syndrome pregnancies, regardless of whether the women had previously undergone invasive testing.
But the publication is not the first to report on the use of genomic sequencing of maternal blood samples for prenatal Down syndrome diagnosis. This October, a team of researchers from Stanford University led by Stephen Quake published a paper in PNAS demonstrating that they could detect fetal Down syndrome and other trisomies by sequencing fetal and maternal DNA in a mother’s blood sample and assessing the relative amount of sequence from each chromosome (see In Sequence 10/14/2008).
The intellectual property surrounding the technologies is uncertain given that both teams have claimed patents related to the techniques described in their respective papers.
Seven authors on the Lo-led paper have reportedly filed patent applications related to the detection of fetal nucleic acids in maternal blood using non-invasive techniques, and Sequenom said last week that it has licensed exclusive rights to the massively parallel genomic DNA sequencing test used in the Lo-led study.
Meanwhile, Quake and Stanford colleague and co-author Christina Fan filed for a patent related to the technology used in their own paper. “I think everything in this [new Sequenom] paper is covered by my patent,” Quake told In Sequence’s sister publication GenomeWeb Daily News last week.
Also last week, Fluidigm said that it has secured co-exclusive licenses to the Stanford researchers’ approach for assessing fetal genetic characteristics from fetal DNA in maternal blood using digital PCR and high-throughput sequencing. The licenses reportedly cover the use of fetal genetic screening by digital analysis, non-invasive fetal aneuploidy diagnosis by sequencing, and digital PCR-enabled prenatal diagnosis.
Quake, who is a co-founder of Fluidigm and chair of its scientific advisory board, said that Fluidigm and a prenatal diagnostic company that did not yet wish to be identified had obtained co-exclusive licenses to the IP.
Fluidigm spokesman Howard High told GWDN last week that the company took the opportunity to secure rights to an important piece of intellectual property as part of its ongoing effort to ensure that its customers have access to important research tools. High emphasized that Fluidigm’s current focus is on providing tools to those involved in research. “We’re a company right now that services researchers,” he said. “We’re not a diagnostic company as such.”
Meanwhile, Charles Cantor, Sequenom’s CSO and co-author on last week’s PNAS paper, told GWDN that Sequenom’s patents, based on Lo’s research over the past decade or so, “cover the application of circulating fetal RNA and DNA for the purposes of non-invasive prenatal testing regardless of the platform used.”
The major difference between the papers, according to Sequenom, is that its own research establishes the effectiveness of a non-invasive, massively parallel genomic sequencing test before any invasive procedures, such as amniocentesis. In contrast, the Stanford paper relied on blood samples taken from women who had undergone such procedures relatively recently — which Cantor said may have artificially increased the level of circulating fetal nucleic acids in the women’s blood.
“I think that’s a lot of sleight of hand,” Quake said. He argued that the amount of cell-free fetal DNA he and his team found in maternal blood was not substantially higher than that reported in other papers. “There’s no significant variation.”
The teams also disagree about the diagnostic role for sequencing-based prenatal tests. Although Cantor said the method works very well and is a “wonderful academic achievement,” he said it is still too expensive to use diagnostically.
According to Lo and his co-authors, the cost of sequencing reagents was $700 per sample with an output of 16 samples per week per Illumina instrument. Though both cost and sequencing time are expected to decrease, Cantor said the sequencing-based tests are as much as three years behind non-invasive tests currently being evaluated in a clinical setting.
Sequenom is currently testing its SEQureDx test, which uses Sequenom’s mass spectrometry platform to diagnose trisomy 21 from fetal RNA in maternal blood. If clinical trials are successful, the company plans to commercialize that test next June. The SEQureDx approach is currently several orders of magnitude cheaper than sequencing-based testing, according to Cantor.
The company recently announced that Brown University researchers are starting a 16-month, 10,000 person study of SEQureDx technology for detecting Down syndrome in the first trimester of pregnancy. And Cantor anticipates at least two large clinical trials of the SEQureDx platform, one in which Sequenom researchers are not involved and another, an in-house study, that will help the company get its CLIA lab up to speed.
Cantor speculated that the massively parallel genomic sequencing test could eventually complement more cost-efficient tests such as SEQureDx. For example, he said, sequencing may eventually be used to assess the roughly five to seven percent of cases that are inconclusive following SEQureDx testing.
Quake disagrees. Sequencing is the clear way to do non-invasive prenatal testing, he argued, saying “I think this will become the diagnostic.” He claimed existing noninvasive Down syndrome tests are not very informative and provide variable results depending on the ethnicity of those taking the test.
A clinical study on the sequencing-based method for prenatal diagnosis is ongoing at Stanford University, Quake added. It involves several hundred patients and researchers plan to expand the scope of the study. For example, Quake said they plan to compare Helicos BioSciences' sequencing technology with the Illumina platforms already being used.
Quake, a co-founder of Helicos, said the goal is to begin testing Helicos' sequencing platform for prenatal diagnostics within the next month or so.
But while Quake believes sequencing-based, non-invasive tests will be used diagnostically within three years, Cantor predicted it will take longer. Between now and then, Cantor said, “There will be time to sort out the patent issues, if there are any.”
— By Andrea Anderson; originally published on GenomeWeb Daily News

DOE Joint Genome Institute Releases Soybean Genome Draft Assembly
The US Department of Energy’s Joint Genome Institute has released a complete draft assembly of the soybean genome, the institute said this week.
The project to sequence the soybean, Glycine max, was led by Dan Rokhsar and Jeremy Schmutz of JGI; Gary Stacey of the University of Missouri-Columbia; Randy Shoemaker of the US Department of Agriculture-Agricultural Research Service; and Scott Jackson of Purdue University, and was supported by the DOE, the USDA, and the National Science Foundation. In addition, the United Soybean Board, the North Central Soybean Research Program, and the Gordon and Betty Moore Foundation supported the soybean genome effort.
Schmutz is scheduled to present preliminary results from an analysis of the sequence at the International Conference on Legume Genomics and Genetics in Puerto Vallarta, Mexico this week. The soybean genome sequence can be browsed here. According to analysis, the 1-gigabase soybean genome has as many as 66,000 genes.
In a statement, James Specht, a professor at the University of Nebraska, said “with the advent of low-cost re-sequencing technologies, soybean scientists now have the means to identify sequence differences responsible for yield potential – the most desired of all crop traits, but to date the most intractable.”

USDA, NSF Microbial Genome Sequencing Program Offers up to $10M for FY '09
The National Science Foundation and the US Department of Agriculture said last week that their interagency Microbial Genome Sequencing program will support between 15 and 20 investigators in the coming fiscal year.
The Cooperative State Research, Education, and Extension Service of USDA and the NSF expect to spend around $10 million — each contributing around $5 million — with awards ranging between $100,000 and $1,200,000. The agencies said that fiscal 2009 will be the last year for the program.
Projects will include high-throughput sequencing of genomes of plasmids, viruses, bacteria, archaea, fungi, oomycetes, protists, microeukaryotes, and agriculturally important nematodes.
More information about the Microbial Genome Sequencing Program grants is available here.

Joint Genome Institute Calls for New Bacterial, Metagenomic, Eukaryotic Sequencing Targets
The Department of Energy’s Joint Genome Institute is asking scientists to propose new sequencing projects for its FY2010 Community Sequencing Program
JGI is interested in projects that “address scientific questions within DOE’s mission areas.” The institute plans to support a variety of projects types, including sequencing of bacterial and archaeal isolates, bacterial resequencing projects, metagenomic projects, eukaryotic sequencing, and sequencing of eukaryotic reference genomes. The institute cautions that its “capacity for draft sequencing is far greater than for finishing.”
The program will start taking letters of intent from Dec. 15, and white papers about proposed bacterial and archaeal isolate sequencing projects from January 2009. Letters are due Jan. 30.
Proposed bacterial and archaeal isolates should expand the phylogenetic representation among sequenced organisms, or they should participate in processes directly relevant to DOE missions.
The institute also wants to resequence bacterial isolates for which a reference genome exists. These projects may focus on bacterial community structure, or on understanding gene function in bacteria under selective pressure or in mutagenized strains. JGI also will consider collections of highly related strains from nature that show phenotypic differences related to DOE’s missions, such as lignocellulose degradation, fermentation of sugar substrates, or metabolism of environmental toxins.
Proposals for metagenomic sequencing and analysis are sought for microbial communities that are relevant to DOE’s interests in alternative energy and carbon cycling, including such targets as rizosphere communities, cellulosic biomass degrading communities, communities capable of degrading environmental toxins, or marine terrestrial communities important in global carbon cycling. These individual projects should be driven by specific project goals rather than environmental surveys, and they could include gene or pathway discovery or complete genome assembly.
JGI also will seek proposals for large-scale eukaryotic resequencing efforts that are appropriate for new short-read sequencing technologies. These could include targets such as biomass feedstocks, model organism plants, biomass degrading fungi, and plant pathogens for which a reference genome exists or is currently planned.
DOE also wants to obtain target genomes of eukaryotes less than 250 megabases in size that are appropriate for sequencing on new technology platforms. Ideal candidate genomes should be inbred, DOE said, and should have minimal polymorphism and repeat content. If some of this information is not yet available, applicants also may propose pilot-scale sequencing in order to acquire the basic genome information.
More information about the sequencing program is available here.

Biomatters Partners with Univ. of Queensland on Metagenomic Sequencing Software
The University of Queensland will work with New Zealand software company Biomatters to develop metagenomic sequencing data analysis software, Biomatters said last week.
Biomatters said it will work with the university on research funded by the Australian Research Council to further develop the company’s Geneious software. The multi-year partnership will aim to “further develop special tools within Geneious that will give biologists the power to use next-generation sequence data for significantly furthering biomedical, agricultural, and environmental research,” Biomatters CEO Candace Toner said in a statement.
The company said the collaboration will develop algorithms for bacterial metagenomics, and the university will use sequencing instrumentation from Applied Biosystems and Illumina.
“The lack of adequate visualization tools for biological research is a major impediment to progress for researchers interested in analyzing the vast data output from the new sequencing technologies now available,” University of Queensland Professor David Edwards said in a statement.

Naval Medical to Purchase Titanium Reagents for GS FLX
The Naval Medical Logistics Command intends to purchase Titanium sequencing reagents and consumables for the 454 FLX sequencer from Roche.
According to a presolicitation notice published on the Federal Business Opportunities website last week, the Naval Medical Logistics Command “intends to negotiate on a sole source basis” with Roche Diagnostics as the provider of Titanium reagents and consumables for the 454 FLX sequencer “to meet the requirements” of a project funded by the Defense Threat Reduction Agency.
The notice, which lists the Navy Medical Research Center in Silver Spring, Md., as the contracting office, did not include financial terms of the proposed agreement.

Doctors' Network to Offer Navigenics' Genotype Test
Navigenics will provide its genomic testing service through a network of physicians in order to help their patients learn about potential genetic risks for certain diseases, Navigenics said this week.
Under the agreement, Navigenics will provide its services to doctors in the MDVIP network, which is spread across 25 states and Washington, DC. These physicians practice preventive, proactive, and personalized healthcare, the company said.
The Navigenics test will be used to identify markers that could indicate a patient’s genetic risk levels for developing conditions such as type 2 diabetes, cancer, heart attack, and celiac disease.
Navigenics said it spent six months working with MDVIP studying how doctors and patients integrated preventive genomics in more than 40 clinical encounters.
The network of 280 doctors, which serves over 100,000 patients, will discuss the testing process with patients. Patients may also consult with a genetic counselor, and Navigenics will conduct the genome scanning and personal risk analysis.

The Scan

Octopus Brain Complexity Linked to MicroRNA Expansions

Investigators saw microRNA gene expansions coinciding with complex brains when they analyzed certain cephalopod transcriptomes, as they report in Science Advances.

Study Tracks Outcomes in Children Born to Zika Virus-Infected Mothers

By following pregnancy outcomes for women with RT-PCR-confirmed Zika virus infections, researchers saw in Lancet Regional Health congenital abnormalities in roughly one-third of live-born children.

Team Presents Benchmark Study of RNA Classification Tools

With more than 135 transcriptomic datasets, researchers tested two dozen coding and non-coding RNA classification tools, establishing a set of potentially misclassified transcripts, as they report in Nucleic Acids Research.

Breast Cancer Risk Related to Pathogenic BRCA1 Mutation May Be Modified by Repeats

Several variable number tandem repeats appear to impact breast cancer risk and age at diagnosis in almost 350 individuals carrying a risky Ashkenazi Jewish BRCA1 founder mutation.