Helicos Receives $10M Under Amended GE Loan Agreement
Helicos BioSciences said this week in a filing with the US Securities and Exchange Commission that it has received $10 million under an amended loan agreement it originally signed with General Electric Capital Corporation and other lenders in December 2007.
The original agreement entitled Helicos to borrow up to $20 million. The company received an initial $10 million at the time, along with the option for an additional up to $10 million through June 30, 2008.
The first $10 million was to be amortized over 36 months, and Helicos owed interest-only payments over the first 12 months of the loan. Under the amended agreement, signed June 27, Helicos received a second $10 million loan with payments of principal and interest due in 36 monthly installments.
In line with the amended agreement, Helicos paid GE Capital a fee of $150,000 to serve as agent for the credit facility, and issued warrants for the rights to acquire up to 110,000 shares of its common stock for an exercise price of $4.80 per share.
The $10 million loan, which was subject to a number of conditions, will help the company improve its cash position. As of March 31, the company had $37.9 million in cash and a “core cash burn” of approximately $3.6 million per month (see In Sequence 5/6/2008).
Applera Becomes Applied Biosystems after Celera Completes Split
Applera said this week that it has changed its name to Applied Biosystems, following its split from Celera. Its stock will continue to be listed on the New York Stock Exchange under the symbol "ABI."
Celera, meantime, is now trading as an independent publicly traded firm on the Nasdaq exchange under the ticker symbol “CRA.”
Celera said that its board has decided to align the company’s fiscal year, which currently ends June 30, with the calendar year. As a result, the company expects to issue its financial guidance for the remaining six months of calendar 2008 when it reports earnings for the fiscal year ended June 30, 2008.
Celera CEO and president Kathy Ordonez said in a statement that the company plans to launch its first offering as an independent company — a testing service for the gene variant KIF6, which is associated with risk for heart disease and statin benefit — “in the coming weeks.”
Invitrogen Teams with Canadian Researchers for Targeted Medical Resequencing
Invitrogen said this week that it will collaborate with researchers at Genome Quebec and the Montreal Heart Institute Pharmacogenomics Centre to develop novel methodologies and reagents for targeted medical resequencing.
Researchers at the Pharmacogenomics Centre are trying to identify new SNPs within around 200 specific ADME/Tox-related genes that affect drug metabolism. The collaboration with Invitrogen is meant to accelerate this effort, the partners said in a statement.
“This collaboration offers Invitrogen the opportunity to work closely with thought leaders in the field of pharmacogenomics and to better understand this emerging area of research,” said Rob Bennett, Invitrogen’s vice president of advanced sequencing applications, in a statement.
Austria’s Blood Center Linz Purchases 454 Sequencer
Roche announced last week that the Blood Center Linz, an Austrian research institute specializing in bone marrow and stem cell transplantation, has purchased a Roche 454 Genome Sequencer FLX.
Blood Center Linz plans to use the sequencer to help match donors with recipients and to assist in research aimed at reducing the risk of rejection during bone marrow and stem cell transplants.
Successful tissue matching involves typing regions of the human leukocyte antigen system, or HLA, to determine whether tissue donors and recipients share enough HLA to prevent the donor’s immune system from attacking or rejecting transplanted tissue. This matching can be difficult and time-consuming and the chances of finding a suitable stem cell donor are just one in 500,000.
By using the GS FLX, the Austrian institute hopes to increase the efficiency of HLA typing, cut the amount of time it takes to find an appropriate donor, and decrease the incidences of tissue rejection by making better donor-recipient matches.
“The continuous decoding of genetic characteristics offers unprecedented insights and opportunities in the area of medical research,” Christian Gabriel, Blood Center Linz’s medical director, said in a statement.
According to Roche, the center is the first non-university institution in Austria to use 454 sequencing and is receiving government assistance to help purchase the instrument.
Mars, USDA, IBM to Collaborate on Cocoa Genome Sequencing Project
Researchers from the United States Department of Agriculture, IBM, and candy maker Mars are collaborating to sequence the cocoa genome, Mars said last week.
The project is expected to take about five years, with researchers at the USDA’s Agricultural Research Service and Mars carrying out some sequencing and related research at a USDA-ARS facility in Miami. For their part, collaborators at IBM’s TJ Watson Research Center in Yorktown Heights, NY, plan to contribute the computing power necessary for assembling and analyzing the sequence data.
Unlike other crop plants such as wheat, rice, or corn, relatively little genetic research has been done on cocoa, which provides the main ingredient in chocolate. Over the past decade or so, collaborations between Mars and the USDA-ARS have focused instead on traditional cocoa breeding projects.
The USDA has also collaborated with other groups in the past, such as the French Agricultural Research Centre for International Development, the University of Reading in the UK, and other groups to better understand cocoa genetics. Previous work has included efforts to develop high-density linkage maps of cocoa genes and compile information on quantitative trait loci.
The cocoa genome project is intended to facilitate the development of cocoa plants with higher yield, better pest and disease resistance, and other desirable traits. The boost to traditional plant breeding, in turn, is expected to help breeders come up with new types of cocoa specialized to certain environments and better quality cocoa.
“Once its genome is sequenced, it has the potential to provide positive social, economic, and environmental impact for the more than 6.5 million small family cocoa farmers around the world,” Public Intellectual Property Resource for Agriculture Executive Director Alan Bennett said in a statement. Some 70 percent of the world’s cocoa supply originates in Africa.
Mars is providing $10 million in financial backing for the sequencing project. The sequence information will be made freely available as it is obtained through the PIPRA web site.
Wellcome Trust Case Control Consortium to Use Illumina BeadChips to Study 90K Samples
Scientists in the Wellcome Trust Case Control Consortium 2 will use Illumina’s Infinium HD BeadChips in a large-scale project to identify genetic variants linked to a number of diseases, including multiple sclerosis, schizophrenia, and asthma, the company said this week.
Illumina said the Wellcome Trust-funded initiative, which comprises the WTCCC2 and 12 independent consortia, will analyze 90,000 DNA samples for both SNPs and copy number variants.
The company said that the proposed series of genome-wide association studies is “collectively the world's largest genetic research initiative conducted to date.”
In addition to the 90,000 samples collected from study participants, the researchers will collect 6,000 control samples that will be analyzed using Illumina's Infinium HD Human1M-Duo BeadChip.
Researchers involved in the initiative expect to generate 120 billion pieces of genetic data over the coming two years, the company said.
Financial terms of the agreement were not released.
Sequenom Prices Public Offering at $15.50 Per Share
Sequenom last week priced its public offering of 5.5 million shares at $15.50 per share. The offering price is higher than the estimated price of $14.25 listed in its preliminary prospectus earlier last week.
All of the shares are being offered by Sequenom. The underwriters of the offering have an option to purchase an additional 825,000 shares.
Lehman Brothers and UBS Investment Bank are joint book-running managers for the offering, with Leerink Swann, Lazard Capital Markets, Oppenheimer, and Rodman & Renshaw acting as co-managers.
Sequenom said last week that it will use funds raised in the offering to develop diagnostic tests for use on its MassArray system and other platforms, as well as for general corporate purposes. The firm also said it may use the proceeds to acquire or invest in other business, “although we have no current plans, commitments or agreements with respect to any acquisition,” as of last week.
Knome Among Genetic Testing Companies Caught in Consumer Genomics Crackdown
Personal genome sequencing company Knome is among 13 genetic testing companies that the California Department of Public Health recently told to stop offering services in the state. Last week, the CDPH released the names of the companies.
The state notified the firms two weeks ago that they must cease and desist from offering the tests to California residents. The companies violate state regulations that these tests must be ordered by a physician and that the labs running the tests must be licensed by California, according to CDPH.
Companies that have already confirmed that they have received letters include 23andMe, DNATraits, Navigenics, and DeCode Genetics. Other firms that have received the letters include Knome, which offers full genome scans at $350,000 a shot, and HairDx, which offers a genetic test to predict baldness.
Knome, which was co-founded by Harvard University geneticist George Church, aims to be a genomics equivalent of low-orbit space tourism flights by offering full genome scans to the wealthy first and developing the technology to bring the price down in the future.
Another company told to stop selling its services to Californians is Gene Essence, which uses an Affymetrix array to identify SNPs a customer has for certain conditions. New Hope Medical, also named by CDPH, is a clinic that provides “diagnostics and therapies not readily available in conventional medicine,” according to its website, and it offers genomic testing for between 12 and 25 SNPs linked to certain conditions for between $475 and $900.
Also included among the 13 firms are CGC Genetics, Salugen, Sciona, Smart Genetics, and Suracell.
Knome told GenomeWeb Daily News in a statement that it has not yet responded officially to California, but said it is seeking “an ongoing dialogue” with the state.
“Our clients have a physician involved throughout the entire process, allowing us to deliver a more robust analysis and ensuring that our clients are supported by a knowledgeable advocate,” the company said. Knome did not respond directly to California’s charge that it is not in compliance with the state’s lab licensing regulation.
By going after consumer genomics companies, California followed a trail blazed by New York, which in April sent similar letters to 23 companies saying that they needed to obtain a permit to offer their services to state residents.
“Any laboratory offering genetic tests to California residents must be licensed as a clinical laboratory in California and have a federal Clinical Laboratory Improvement Amendments (CLIA) certificate for laboratory testing,” CDPH spokeswoman Lea Brooks told GenomeWeb Daily News in an e-mail.
Brooks also said the doctor oversight rule is clear. “In California, all genetic tests must be ordered by a licensed physician.”
California officials took action after they investigated a total of 25 firms “in response to numerous consumer complaints about the accuracy and cost of genetic testing advertised on the Internet,” Brooks added.
Peter Kazon, a lawyer with Allston & Bird who has specialized in medical diagnostics regulatory affairs, thinks that beyond licensing and doctor oversight concerns, a background issue that could become important is the larger question of exactly what these companies are selling. If a company's service informs a customer that they have a genetic variant that puts them in a broad risk category for cancer or Alzheimer’s, the product is that information, he said.
One aspect of the California action, Kazon added, is that the regulators want to know what the science is behind these services’ claims and how those claims are communicated to patients.
“California is saying this is healthcare information, and not just saying, ‘Am I related to Barack Obama in my distant past?’ You’re telling people healthcare information,” he said.
The potentially complicated issue Kazon sees springs from a section of the state law that was adopted from a US Code of Federal Regulation. That section states that these kinds of tests must have established performance specifications for a number of factors, including accuracy, precision, analytical sensitivity, analytical specificity, and others.
— Adapted from an article by Matt Jones, originally published on GenomeWeb Daily News
House Considers $1.2B Boost to Bush's '09 NIH Budget
The National Institutes of Health would receive a $1.2 billion increase over this year in 2009 under a budget proposal being considered last week by the House Appropriations Committee.
Representative David Obey (D – Wis.), who chairs the committee and the subcommittee on Labor, Health and Education, and who submitted the proposed budget for next year, said the additional funding would make up for what he called constraints placed on Congress by the Bush administration’s “short-sighted priorities.”
President George W. Bush in February proposed a total of $29.5 billion for the NIH in fiscal 2009 in the administration’s budget.
The proposal would approve a total of $30.1 billion, compared to the $28.9 billion the NIH received in fiscal 2008.
Among a number of other funding increases for Medicare, state insurance pools, and vocational education, the increased appropriation would allow the NIH “to capitalize on unprecedented scientific opportunities that reduce the disease burden on the country,” Congressman Obey said in a statement two weeks ago.
“In all my years in Congress, I’ve never had anybody come up to me and say, ‘Obey, why don’t you guys get your act together and cut cancer research?’ And yet, that’s what happened over the last two years,” Obey continued.
The Federation of American Societies for Experimental Biology, a group that has criticized the White House’s budget proposal and has asked for Congress to approve $31.2 billion for the NIH, cheered the new proposal.
“Years of flat funding have been discouraging to researchers and have delayed the progress of life-saving discoveries,” FASEB President Robert Palazzo said in a statement.
Bird Phylogeny Reveals Unexpected Relationships
A new large-scale study is altering scientists’ understanding of the evolutionary relationships between different types of birds.
In a paper appearing online in Science last week, a team of American researchers sequenced thousands of bases of DNA from each of nearly 170 bird species. Based on their phylogenetic analyses of these birds, which represented all the major living bird groups, the team found evidence to support some previously held views of bird relationships. But other findings revealed unexpected relationships between birds and provided new insights into the evolution of specific bird traits, behaviors, and lifestyles.
“What we wanted to do was provide ourselves — and the rest of the research community — with the roots and the trunk and the tops of the tree of life for birds,” co-lead author Shannon Hackett, associate curator of birds at the Field Museum of Natural History in Chicago, told In Sequence’s sister publication GenomeWeb Daily News.
Many people think of birds as being very well-studied, co-lead author Rebecca Kimball, a zoologist at the University of Florida, told GenomeWeb Daily News. Indeed, she said, there are numerous studies on bird morphology, behavior, ecology, and genetics — though many of these have focused on just one or two genes.
Even so, evolutionary relationships between the majority of bird species have remained murky, with little consensus among researchers about which species are most closely related, Kimball said, adding that some have suggested that bird phylogeny is an unanswerable question.
Undeterred, Hackett, Kimball, and their co-workers from across the US took a genome-wide view in order to try to understand evolutionary relationships between bird species. As part of the Early Bird Assembling the Tree of Life Research Project, the team spent more than five years sequencing and comparing DNA from representatives from all of the main living bird groups.
To do this, they chose species based on their perceived genetic distance from one another determined from previous studies, Hackett said, with the goal of representing each major genetic lineage. These samples were housed at museums and other participating institutions, Kimball said.
All told, the group sequenced an estimated 32 kilobases of nuclear DNA — containing information from 15 different chromosomes — for each of the 169 bird species tested. These included a few protein-coding regions, though the team purposely focused on non-coding regions, particularly introns.
“We targeted sort of regions that evolved more quickly and were under less evolutionary constraint,” Kimball explained. Because the introns are under relatively little selection, they are prone to more sequence differences.
“That was pretty controversial,” Hackett added. That’s because some thought the introns would be too divergent to align. For the most part, though, the researchers were able to align the sequences and make good predictions about evolutionary relationships.
Using this approach, they were able to confirm some previously proposed but hotly debated relationships between birds — including a close link between flamingos and grebes. On the other hand, their findings also revealed some new and unexpected relationships. For instance, they found that a large group of birds called Passeriformes (perching birds or songbirds) were closely related to parrots.
They also discovered unexpected splits within bird groups that were heretofore believed to be related. This included splits within the raptor group, predatory birds such as hawks, eagles, and falcons that look and act similarly. Their results suggest that falcons are not closely related to eagles and hawks.
And, despite their similar prey preferences, owls aren’t closely related to the other raptors, either. “We probably have at least three different evolutions of this lifestyle,” Kimball said.
Notably, they also found that birds with other specialized lifestyles — including water birds and nocturnal birds — evolved several times. “We’re getting a much better idea about how many times these habitats and lifestyles have evolved,” Hackett said.
Knowledge of these phylogenetic relationships is expected to inform other types of research — on everything from species morphology to ecology — as well. That, in turn, could help biologists, conservationists, and others predict how certain birds will adapt to environmental or ecological challenges. “Understanding how a bird species responds, in part, is facilitated by understanding what it’s related to,” Kimball said.
Despite the new resolution provided by this study, there are still some “thorny issues” at the base of the bird tree of life, Hackett said. The team is currently going back to the most surprising relationships and examining them in more detail by looking at additional representative species and/or by more gene regions. “We are looking at what would happen if we collected much more data,” Kimball said.
— By Andrea Anderson, first published on GenomeWeb Daily News
Polygenic Analysis May Aid Breast Cancer Diagnosis
Combining traditional breast cancer screening with genetic risk assessment programs based on several alleles has the potential to improve diagnoses, new research suggests.
While much has been done to suss out genes that increase breast cancer risk, questions remain about how much diagnostic information common risk alleles provide. In a paper published in last week’s New England Journal of Medicine, a team of researchers from the United Kingdom analyzed a handful of these alleles to better understand their use, if any, in disease prevention. Their findings suggest that moderate-risk alleles may help delineate populations of women who require earlier or more vigilant screening.
Although many of the causes of breast cancer are still unknown, the disease often runs in families and is at least partly heritable. The most well-known single genes associated with high increases in breast cancer risk are BRCA1 and BRCA2.
But just a quarter of inherited breast cancer can be explained by such rare single mutations. And while it’s known that having several more common moderate-risk alleles can compound an individual’s overall risk of breast cancer, the overall usefulness of these genes for predicting cancer risk is poorly understood.
To address this, senior author Bruce Ponder, an oncology researcher at the University of Cambridge, led a team of researchers interested in determining the significance of common alleles, if any, for diagnosis and breast cancer prevention. They focused on seven recently discovered alleles that are thought to confer moderate increases in cancer risk, based on genome-wide SNP studies.
Their analysis suggests that some 58 percent of breast cancer cases occur in women who are at the upper half of a risk distribution curve delineated by the seven risk alleles tested. At the far end of this curve, the ten percent of women with the highest risk represented 15 percent of breast cancer cases.
Those results suggest that the common alleles tested cannot necessarily be used as a prevention tool in individuals, but may be useful for identifying populations at increased risk that will benefit from closer scrutiny, including earlier mammography. Rather than using mammography screening on every woman over 50 years old, for instance, the researchers suggested that each woman’s breast screening should start at an age appropriate for her risk group — be it 40 years old or 60 years old.
“It would be possible to genotype every woman at all known susceptibility loci and, on the basis of her breast-cancer risk profile, offer a personalized screening program in which the starting age would vary,” Ponder and his team wrote.
And, they predicted, as more research turns up new risk alleles, the risk estimates within populations should continue improving. In addition, the researchers said, integrating information about other, individual lifestyle risks could further improve this prediction model.
“Although the clinical use of single, common low-penetrance genes is limited, a small number of susceptibility alleles could distinguish women at high risk for breast cancer from women at low risk, particularly in the context of population-screening programs,” the authors wrote.
Still, they noted that “[m]ost reported genetic associations have been false positive results and would be worthless for risk prediction.” Consequently, they emphasized the need for a solid understanding of susceptibility loci and the risk associated with each.
In an accompanying perspectives article published in the same issue of NEJM, Harvard researchers David Hunter and David Altschuler and University of Pennsylvania researcher Daniel Rader agreed that interpreting the risk associated with common alleles is promising but requires much more research and clinical validation.
“Our challenge will be to develop research methods that take us from genetic localization to medically useful application, as well as to support investigators who want to seize this opportunity and translate it into greater understanding of disease and better care for patients,” Hunter and his colleagues concluded.