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Beijing Genomics Institute; CLC Bio; Wellcome Trust Sanger Institute; Barts and The London School of Medicine and Dentistry; 454; Roche NimbleGen; ECBoL; MPI for Molecular Genetics; Indiana University; University of Arizona; University of Minnesota; Secre

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BGI to use CLC Bio's Sequencing Analysis Software
 
The Beijing Genomics Institute has licensed CLC Bio’s sequencing analysis and visualization software, CLC Bio said last week.
 
The site license agreement for CLC Bio’s Genomics Workbench allows all BGI researchers to use the software in all of its sites, inside and outside of China.
 
The Aarhus, Denmark-based company said BGI will use the software in its daily research, which includes projects such as the Giant Panda Genome Project and the 1000 Genomes Project.
 
Ruiqiang Li, head of BGI’s bioinformatics division, said in a statement that the institute chose CLC Genomics Workbench for analyzing next-gen sequencing data “after testing several commercial solutions.”
 
BGI has 17 Illumina Genome Analyzers, two ABI SOLiD sequencers, and three Roche 454 sequencers in its next-generation sequencing tool shed.
 
CLC Bio said the Genomics Workbench utilizes paired-end data and supports tasks including reference assembly, de novo assembly, SNP detection, multiplexing, and high-throughput trimming.
 

 
Wellcome Trust Sanger Institute Generates Terabase of Sequence Data In Six Months
 
The Wellcome Trust Sanger Institute has generated a terabase of sequence data over the last six months, the institute said last week.
 
The data were produced for projects like the 1000 Genomes Project, the institute’s Cancer Genome Project, and pathogen sequencing projects.
 
The Sanger Institute currently generates 50 terabytes of quality-filtered sequence data per week, using sequencing instrumentation from Roche/454, Illumina, and Applied Biosystems.
 

 
Barts and the London School of Medicine and Dentistry Aquires 454 GS FLX,
Roche NimbleGen Capture Array Technology to Study Leukemia
 
The School of Medicine and Dentistry at Barts and The London, a UK-based hospital teaching trust, has acquired a Roche 454 Genome Sequencer FLX as well as Roche NimbleGen sequence capture array technology, Roche said this week.
 
The school’s cancer genomics group, led by Brian Young, plans to use the system to study genetic changes involved in the development of leukemia. The researchers plan to link the sequence information to an existing clinical and cytogenetic database to investigate the relationship between genetic changes and clinical features of the disease.
 
The researchers expect that the new data could have implications for the future therapy and clinical outcome of hematological malignancies.
 
Using the Roche NimbleGen arrays, the researchers plan to capture a number of genes, including those known to be mutated in acute myelogenous leukemia, such as FLT3 and MLL, and characterize putative mutation targets by SNP genotype analysis. They also plan to analyze full sequences of mutated genes, including introns, using the GS FLX.
 
The scientists also want to study patterns of microRNA expression in AML and compare them to known gene expression profiles for other leukemia subtypes.
 
In addition, they plan to use paired-end sequencing to study microdeletions, a type of genetic abnormality that appears to be a characteristic feature of leukemias.
 

 
European Initiative Plans to Barcode 100,000 Species Over 5 Years
 
A European initiative, dubbed ECBoL, plans to establish a network of laboratories among major biodiversity resource centers in Europe that will join the International Barcode of Life initiative.
 
The planned network will be capable of generating DNA barcodes at an industrial scale, and plans to initially barcode a million specimens within five years, representing 100,000 species.
 
Pedro Crous, director of the CBS Fungal Biodiversity Centre in Utrecht, the Netherlands, will present details about ECBoL, which is hoping to raise $25 million, at a meeting in Strasbourg in September.
 
“We have amazing collections in museums and herbaria that have been gathered over the past centuries – the lion’s share of all the species known on Earth are represented in European collections,” Crous said in a statement. “We also have a strong tradition of taxonomy, so we are in a uniquely powerful position to make a real impact in this field.”
 
“What we want to achieve at the EuroBioFund meeting is to get commitment from industry and governments that support biodiversity research to commit to this European barcoding campaign.”
 
One of the goals of ECBoL will be to develop a hand-held DNA barcoder. Portable sequencing technology and wireless technology for transmitting sequence data are already available, according to Crous, but sample preparation still needs to be miniaturized.
 
ECBoL will be part of the International Barcode of Life initiative, which was proposed by Canadian scientists and is currently seeking to raise CAN$150 million (US$147 million) to barcode 500,000 species over the next five years.
 

 
RNA-Seq Study Provides Insights into Alternative Splicing in Human Cells
 
In a paper published online last week in Science, German researchers used high-throughput RNA sequencing, called RNA-Seq, to map and compare the transcriptomes in two different human cell types.
 
In the process, they uncovered new transcriptional units and obtained an unprecedented picture of the type and frequency of alternative splicing events in these cells.
 
Senior author Marie-Laure Yaspo, a researcher at the Max Planck Institute for Molecular Genetics in Berlin, told In Sequence’s sister publication GenomeWeb Daily News that this improved view of alternative splicing was possible because the RNA-Seq approach gives a “really direct readout of the splicing event.”
 
It’s been long known that cells use alternative splicing to create different RNA transcripts from the same stretch of DNA. But, Yaspo said, until now there were no good tools to directly examine this alternative splicing. “What is known had been known by inference,” she said. For example, in the past, some researchers predicted splicing events from expressed sequence tag analysis and similar studies.
 
For this study, the researchers used RNA-Seq to investigate both gene expression and alternative splicing in the same data set. “That’s the beauty of this method,” Yaspo said. Indeed, several recently published studies have successfully employed RNA-Seq to decipher the transcriptomes of human cells, mice, Arabidopsis, and yeast.
 
Yaspo and her colleagues compared the gene expression and splicing profiles in two cell lines: human embryonic kidney cells and human B cells. They selected these cell lines because they were very distinct from one another and, therefore, expected to exhibit very different expression and splicing profiles, Yaspo explained. For each cell type, the researchers used the Illumina Genome Analyzer to sequence complementary DNA derived from polyadenylated RNA.
 
Using this approach, they detected roughly 10,000 to 12,000 transcribed genes in each cell type — about 25 percent more than detected by microarrays. Of these, about 66 percent corresponded to known genes, while the remaining 34 percent represented non-annotated genes. RNA-Seq analysis revealed nearly 4,440 genes whose expression varied by cell type.
 
The team also identified 94,241 splice junctions — including more than 4,000 new splice ones — in about 3,106 genes. In both cell types, they found that exon skipping was the most common form of alternative splicing, though they also detected lower levels of alternative 5’ and 3’ splicing.
 
“We were able to find novel junctions that weren’t seen before,” Yaspo said, something that would have been more difficult or impossible based on splicing predictions alone. “There’s a difference between predictions and a direct readout,” she emphasized.
 
In the future, Yaspo said, she and her co-workers plan to do similar experiments in additional cell types. Another step, she added, will be looking at gene expression and splicing data together, to get an idea of how the two are related in different cell types.
 
“I am intrigued and fascinated by this alternative splicing that we can see so clearly by this [RNA-Seq] method,” she said.
 
By Andrea Anderson; originally published on GenomeWeb Daily News
 

 
Whole-Genome Sequencing Uncovers Nature of Yeast Spontaneous Mutations
 
In a paper that appeared online in the Proceedings of the National Academy of Sciences last month, a team of American researchers used 454 pyrosequencing to detect spontaneous mutations in four Saccharomyces cerevisiae lines. The work is providing a whole-genome view of the small and large mutations that tend to arise in yeast — findings that can inform comparative studies between organisms and, more broadly, improve scientists’ understanding of evolution.
 
“Mutation provides the resources on which natural selection can act,” lead author Michael Lynch, a biologist at Indiana University, told In Sequence’s sister publication GenomeWeb Daily News last week. “To me, that’s sort of the bottom line for understanding evolution.”
 
Despite the fact that spontaneous mutations influence everything from evolutionary genetics to inheritance and genetic disease, scientists still know relatively little about the frequency and nature of such mutations, particularly on a whole-genome level.
For this study, Lynch and his co-workers used 454 pyrosequencing to sequence four haploid lines of the model organism S. cerevisiae. The lines were derived from the same parent strain and put through single-cell bottlenecks for three to four days or roughly 200 cell cycles.
 
About half the genome yielded sequence data that was sufficient for analysis. Overall, the researchers found a genome-wide mutation rate of roughly 0.32 per cell division.
 
The per-base mutation rate was not much different from that reported previously using different methods, Lynch noted. And most of the small-scale mutations detected were base-substitutions.
 
Of the 33 base-substitutions detected, G/C to A/T mutations occurred more often than mutations in the other direction. On the other hand, the researchers detected just one single-base-pair deletion and one three-base-pair inversion.
 
More unexpectedly, the nuclear genome actually had a very high rate of large mutations more than a thousand base pairs in size, especially segmental duplications and deletions. Indeed, Lynch noted, the whole-genome view uncovered as many large mutations as it did point mutations.
 
The researchers also noticed some unusual events during microarray and sequencing experiments, Lynch said. For instance, during sequencing they got much higher coverage than anticipated for some parts of the genome, while those regions with lower coverage yielded about half as much information as expected.
 
Based on these and other observations, the researchers concluded that the haploid yeast cells were actually diploidizing over time — a phenomenon previously reported.
 
“Most of the time when you think you’re dealing with a haploid line, you’re probably dealing with a diploid,” Lynch said. “[The yeast] clearly like to be diploid.” What drives this diploidization and how it occurs is still largely unknown, though Lynch noted that individual chromosomes seem to diploidize individually, such that the whole genome doesn’t seem to become diploid at once.
 
More research is necessary to get a genome-wide view of mutation rates in other organisms. But preliminary comparisons presented in the paper suggest the yeast nuclear mutation rates are comparable to those observed in Drosophila and humans. C. elegans, on the other hand, appears to have a much higher mutation rate, based on PCR analysis and sequencing of limited regions of the genome.
 
The team is currently using the whole-genome sequencing approach to understand spontaneous mutation in other organisms, such as a type of paramecium, the water flea Daphnia, and Arabidopsis.
 
Lynch said the team is also interested in understanding how specific mutations — for example, in mismatch repair genes or polymerase genes — affect spontaneous mutation rates. “I think we’ll be able to do that in the not too distant future,” he said.
 
By Andrea Anderson; originally published on GenomeWeb Daily News
 

 
Study Assesses Eukaryotic Tree of Life
 
More and better organism sampling aimed at achieving greater genomic depth will be necessary to flesh out the tree of life, a new analysis suggests.
 
In a paper appearing online in Science last week, University of Arizona evolutionary biologist Michael Sanderson assessed the current state of the eukaryotic tree of life, looking at the phylogenetic signal present. He discovered that while there is a relatively strong signal for well studied groups, such as vertebrates and non-vertebrate animal models, the information available for the other eukaryotes is very broad and mostly insufficient for creating one unified tree of life.
 
In the article, Sanderson argued that creating a eukaryotic tree of life remains a lofty, but ultimately achievable goal. “Construction of a high-resolution phylogenetic tree containing all eukaryotic species in the database is a grand challenge that is substantially more tractable than inferring the entire tree of life,” he wrote, “but to succeed, strategies will have to overcome serious sampling impediments.”
 
First, though, Sanderson emphasized the need for understanding the strength and distribution of the phylogenetic data that is currently available in the NCBI taxonomy tree. To do this, he looked at the phylogenetic signal found in 1,127 higher taxa representing 14,289 phylogenies and 2.6 million GenBank sequences.
 
The analysis revealed a strong phylogenetic signal for vertebrates — especially humans — and model organisms such as Drosophila. Overall, though, just 12 percent of the operational taxonomic units tested garnered the minimal phylogenetic support used in Sanderson’s analysis.
 
In general, the groups of eukaryotes with more species diversity were slightly less likely to have achieved minimal phylogenetic support. “Some taxa with surprisingly low support exemplify how biological diversity can overwhelm substantial and sustained phylogenetic efforts,” Sanderson wrote.
 
He also noted that the sequence data available so far “are enriched for taxonomic diversity to the relative exclusion of some high-throughput genomics data, which, though presently available for only a small fraction of eukaryotic taxa, ultimately should enable stronger phylogenetic inferences.”
 
In the future, Sanderson predicted that better phylogenetic inference tools will improve the information that can be gleaned from available data, but he also emphasized the need for newer sampling strategies and targeting sequencing projects appropriately.
 
“[S]ampling protocols guided by quantitative assessments of the phylogenetic distribution of data will improve the efficiency of emerging phylogenomic strategies for building the tree of life of known organisms,” Sanderson wrote.
 

 
SACGHS Task Force Sees Consumer Genomics as 'Number One Priority'
 
A US Department of Health and Human Services committee plans to vote in December on the recommendations it will supply to HHS Secretary Michael Leavitt concerning the state of genomics in the US, particularly concerning consumer genetic testing and pharmacogenomics.
 
Paul Wise, who chairs the Secretary’s Advisory Committee on Genetics, Health, and Society’s Priority Setting Task Force, told members of the committee in Washington, DC, this week that the group will likely focus on standards to monitor direct-to-consumer genetic testing because committee members and others, through a public comment period last month, had identified this as the top priority.
 
Wise said this week that after reviewing the various comments, the task force has identified 73 total subjects it will consider. He said that consumer genetic testing was mentioned most overall as “the number one priority” and that it received the most interest from both expert and public comments.
 
Wise expects the task force to winnow this large number of issues down to several cluster areas on which it will vote. Between now and November, the task force will gather information about the issues, develop issue briefs, and submit those materials to the committee.
 
The task force’s vote will come after November, when the US will have a new president-elect that could potentially replace Secretary Leavitt soon after the SACGHS receives the task force’s priorities.
 
Wise acknowledged that it is possible that the committee may be developing its recommendations for the secretary in a different political environment, but he did not elaborate on whether he views that as an important concern for the task force.
 
The specific clusters the task force will look into in the coming months include the need to develop more evidence for personalized medicine; training and education of health professionals in genetics and genomics; evidence-based guidelines for genetic technologies; coverage and reimbursement for genetic services; Medicare and Medicaid reimbursement for DNA tests; and genetics and health disparities among minorities.
 
Wise said that several factors will influence the issues the task force sets as priorities as it advises the committee. Among those are the “urgency and national importance of the issue,” the extent to which the federal government has jurisdiction or authority over the issue, and the “need for federal guidance or regulation over the issue.”
 
By Matt Jones; originally published on GenomeWeb Daily News
 

 
DTC Genomics Firms Respond to Concerns at Fed-Sponsored Roundtable
 
A panel discussion hosted by the US Department of Health and Human Services this week served as a forum for several direct-to-consumer genomic testing firms to address a growing number of scientific, ethical, and regulatory questions surrounding their business models.
 
At a workshop called “Understanding the Needs of Consumers in the use of Genome-Based Health Information Services,” executives from Navigenics, DeCode Genetics, and 23andMe joined representatives from the research community and other interested parties to hash through a number of problems and possibilities facing the quickly evolving field.
 
“Genomics can make the next 10 to 20 years really exciting if we do it the right way,” said Muin Khoury, director of Public Health Genomics at the Centers for Disease Control and Prevention, but he warned that he does not want to see genomics go the way of full-body imaging — an expensive fad with little more than promise backing it up on the clinical end.
 
Khoury earlier this year criticized the burgeoning DTC genetic testing market in the New England Journal of Medicine as a practice that is not ready for public consumption.
 
At this week’s panel discussion, he said that the industry doesn’t have “a good handle on the oversight … or on the analytic performance of these assays.” Currently, he said, “we don’t know if the information we get from one company is the same we get from another company.”
 
As an example, he said that the predicted risk of heart disease based on genetic factors could change if a new marker is discovered.
 
Jim Evans, a molecular biologist at the University of North Carolina at Chapel Hill and editor of the journal Genetics in Medicine, agreed, noting that he is concerned that “mass marketing the appeal of individual genomics takes our eye off the real value of this type of endeavor.”
 
Genome-wide association studies offer “incredible potential” for understanding disease, Evans said, but knowing that you have a 44 percent risk for heart disease versus a 52 percent risk is not enough to be meaningful, and it could lead people to feel they have a free pass to engage in risky behaviors.
 
“Why don’t you think I should be able to do this?” asked health sciences investor and advocate Esther Dyson, who said she has used 23andMe’s service. Dyson said that she has learned a lot from using the service and understands its limitations in making health decisions.
 
Evans responded that consumers “deserve a clear explanation, and not kind of a marketing ploy that this is useful medical information, because it’s really not.”
 
Alan Guttmacher, deputy director at the National Human Genome Research Institute, said he agreed with Evans.
 
“If you read [the companies’ websites] carefully, it’s extremely well worded, but if you walk away from the sites with a general impression, it may not always match what the wording of the site is,” he said.
 
Representatives from the consumer genomics industry were quick to defend their practices. Linda Avey, co-founder of 23andMe, stressed that the company is “giving our customers information about what’s coming out of the research community” — not “clinically validated” information.
 
“We’re really arming individuals with the information of their genomes, but we’re not really focusing on these individual tests. We’re giving our customers information about what’s coming out of the research community,” she explained.
 
She said that the company is looking to gather information from customers that can then be meshed with information from new studies coming out, particularly about adverse reactions to drugs. “We need to work together as a community — no one player in this space is going to make this happen,” she said.
 
Jeffrey Gulcher, chief scientific officer of DeCode, defended against criticisms from Khoury and others that the information from genetic testing is not more valuable than information from family histories, noting that 95 percent of prostate cancer patients do not have a diagnosed case of prostate cancer in their families.
 
Gulcher said he believes genomic information can help “prioritize patients” by putting different information types together. This information could be used to target patients who need earlier intervention, or it could be used to help patients make decisions about changing their lifestyles.
 
These common genetic risk factors are “adding something much beyond family history,” he said. “Family history alone will not substitute for this genetic profile.”
 
He added that the company’s genetic risk tests “are very well clinically validated indeed … if the definition of clinical validity is that you discover them among one population and then you replicate them among multiple populations.”
 
Nancy Johnson, a former Congresswoman and current Senior Public Policy Advisor for Baker Donelson, said the major challenge today is that the “change of pace” of the technology “is so rapid that we have to accelerate the communication between the private sector and regulators.”
 
Mari Baker, CEO of Navigenics, agreed, noting that the private and public sectors need to “work together more aggressively than we have in the past and in a more intelligent fashion, so the industry, if they have any sense, won’t indulge in an explosion of direct-to-consumer advertising.”
 
She also said that the community should look to recent moves by the states of New York and California, which ordered a number of consumer genomics companies to stop offering their tests to residents, “as an opportunity to talk about what they’re doing, and work together to get more standardized tests.”
 
“Transparency and openness will save this industry, but if there isn’t that kind of openness, we will erode that trust,” she added. 
 
By Matt Jones; originally published on GenomeWeb Daily News

The Scan

Fertility Fraud Found

Consumer genetic testing has uncovered cases of fertility fraud that are leading to lawsuits, according to USA Today.

Ties Between Vigorous Exercise, ALS in Genetically At-Risk People

Regular strenuous exercise could contribute to motor neuron disease development among those already at genetic risk, Sky News reports.

Test Warning

The Guardian writes that the US regulators have warned against using a rapid COVID-19 test that is a key part of mass testing in the UK.

Science Papers Examine Feedback Mechanism Affecting Xist, Continuous Health Monitoring for Precision Medicine

In Science this week: analysis of cis confinement of the X-inactive specific transcript, and more.