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Short Reads: Jan 13, 2009


Transitioning to Second-Gen Technologies, JCVI Cuts Staff, Consolidates Sequencing Operations

The J. Craig Venter Institute last month consolidated its sequencing operations into its main campus in Rockville, Md., and eliminated 29 sequencing staff positions as a result.

The not-for-profit genomic research institute shut down its large DNA sequencing facility in Rockville in October, it said in a statement, and moved its sequencing team to its main Rockville campus.

The staff reduction “is a direct result of a technology shift and is not a reflection of the tough economic times that we are all facing in the United States today,” J. Craig Venter, founder and president of JCVI, said in the statement. “JCVI has been awarded in excess of $13 million in competitive grants and contracts in 2008 alone and does not anticipate any additional staff reductions.”

He noted that JCVI, like other sequencing centers, has been replacing its older Sanger sequencing technologies with the latest-generation DNA sequencing machines. “While technological advances bring breakthroughs to many aspects of science, unfortunately they also come at a cost, which is that fewer people are needed to run the large facilities and many machines that were once needed,” said Venter.

A JCVI spokesperson said that the institute has no plans to open any new large-scale sequencing centers.

Expression Analysis Buys Illumina Genome Analyzer, Plans to Offer Ag Services

Expression Analysis said last week that it has purchased an Illumina Genome Analyzer to add to its genomic services.

The Durham, NC-based genotyping and gene-expression services company also said that it plans to diversify its services to include agricultural offerings.

Expression Analysis CEO Steve McPhail said in a statement that client interest in both plant and animal genomic services was key to the decision to acquire the Genome Analyzer. McPhail said the company is the only Illumina-certified service provider to offer all of the Illumina platforms, including the iScan, BeadStation, and BeadXpress, in addition to the Genome Analyzer.

The company also offers genotyping, gene expression, and sequencing services using platforms from Affymetrix, Life Technologies’ Applied Biosystems business, and Helicos BioSciences.

Consortium Uses 454, Illumina Sequencers to Decode Cacao Genome

A consortium of researchers is using sequencers made by Roche 454 and Illumina, and possibly also Sanger sequencing and other methods, to decode the cacao genome, according to a US Department of Agriculture-Agriculture Research Service researcher.

Brian Scheffler, a computational molecular biologist and director of the USDA-ARS Mid-South Area Genomics Laboratory, described the plan to sequence the 400-megabase genome during a workshop at this year's at the Plant and Animal Genome conference, held in San Diego this week.

Last June, the USDA-ARS, along with IBM and candy maker Mars, announced that they were embarking on a five-year study to sequence the cacao genome. At yesterday's session, several individuals involved in the collaboration shed additional light on the project.

Describing the project's decision to use a combination of 454 and Illumina sequencers, Scheffler emphasized the need to balance quality, speed, and cost. He said the team is using several complementary approaches to perform whole-genome shotgun sequencing of the cacao genome, including long- and short-read, high-throughput sequencing.


The researchers plan to use long random-sheared and paired-end reads generated by 454 sequencing, along with short paired-end reads generated on Illumina’s Genome Analyzer. The team will likely also use Sanger sequencing, BAC-end sequencing, and fosmid sequencing to fill in remaining gaps, Scheffler said.

A bioinformatics group at IBM will carry out quality assurance for the project, while researchers at the Department of Energy's Joint Genome Institute will bring their own methods to help assemble and annotate the genome, Scheffler said.

He said the cacao consortium also aims to make data accessible to other research groups and work with cacao breeders and end users.

By Andrea Anderson; originally published on GenomeWeb Daily News

Duke Using Illumina GA to Study HIV Resistance

Duke University plans to use Illumina's Genome Analyzer to search for genetic variations that may enable some people to be resistant to HIV infections, the company said this week.

Researchers at the Center for Human Genome Variation at Duke's Institute for Genome Sciences and Policy will use the technology to sequence the complete genome of at least 50 individuals. The project is supported by a $3 million grant from the Bill and Melinda Gates Foundation.

The study is conducted by Duke University Medical Center and aims to find out why certain individuals exposed to the HIV virus do not become infected with it, the company said.

The DUMC study "represents the first effort to search through the entire human genome for any variants, rare or common, that influence susceptibility to infection by HIV-1," DUMC Director David Goldstein said in a statement.

The DUMC study and the Center for Human Genome Variation's research "will allow us to identify the most important genetic determinants of resistance to HIV-1 and may ultimately point the way toward new therapies to protect against HIV/AIDS," he added.

Illumina Rolls Out Certified Provider Program for Sequencing

Illumina said last week that it has rolled out a new certified service provider program for organizations offering sequencing services on its Genome Analyzer.

The first participants in the program, having passed certification, are the National Center for Genome Resources in Santa Fe, NM, and Geneva-based Fasteris. Both were involved in validating the processes for the CSPro Sequencing Program and developing certification standards, annual audits, and best practices guidelines.

Other providers that are in the early stages of certification include GATC Biotech in Germany, the Beijing Genomics Institute in Shenzhen in China, and Expression Analysis in the US.

The CSPro Sequencing Program is an extension of similar programs Illumina already has in place for its genotyping and gene expression platforms. Participants undergo a “rigorous” two-phase certification and on-site audit of their facilities and processes, said Illumina.

Sequencing Study Detects New Prostate Cancer Gene Fusions

A transcriptome-sequencing study using a combination of long- and short-read sequencing technologies made by Roche’s 454 and Illumina has identified new gene fusions involved in prostate cancer.

In the study, which appears in this week’s online edition of Nature, a team of University of Michigan researchers searched for new gene fusions in prostate cancer by sequencing the transcriptomes of patient cell lines and tumor samples.


"We defined a new class of mutations in prostate cancer," senior author Arul Chinnaiyan, a pathology and urology researcher at the University of Michigan, said in a statement. "The recurrent fusions are thought to be the driving mechanism of cancer. But we found other fusions as well, some of which were unique to individual patients."

In an effort to identify new prostate cancer-related fusions, Chinnaiyan and his colleagues used a combination of long-read sequencing with a Roche 454 FLX and short-read sequencing with an Illumina Genome Analyzer to decode prostate cancer transcriptomes.

Chinnaiyan and his colleagues are reportedly applying a similar approach to search for gene fusions in breast and lung cancers and melanoma.

"Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization," the authors wrote.

By Andrea Anderson; originally published on GenomeWeb Daily News

KeyGene, Amplicon to Offer Genome-Profiling Service

KeyGene and Amplicon Express have partnered to offer an integrated whole-genome profiling service intended to enable researchers to construct a complete de novo physical map of plant and animal genomes "in a fast and cost-effective manner," KeyGene said this week.

KeyGene offers its technologies, databases, and expertise to the plant breeding industry. Amplicon Express sells genomics research products, including custom BAC libraries and BAC DNA-pooling strategies used in second-generation sequencing.

KeyGene and Amplicon Express will combine marketing and sales forces and their technical support teams to offer the service, Amplicon Express's CEO Robert Bogden said in a statement.

KeyGene also said that the method the partners will offer has been used to generate a high-resolution assembly of a 450-megabase melon genome.

NHGRI to Fund Genomics ELSI Centers

The National Human Genome Research Institute has set aside $3.9 million in funding for 2010 to create several cross-disciplinary centers that will study the ethical, legal, and social implications of genomics technologies.

The agency said it plans to launch a new funding program to support the effort, and will give grants of up to $750,000 per year for five years to as many as three specialized centers and exploratory centers and up to $150,000 per year for three years for three exploratory research projects.

NHGRI wants these Centers for Excellence in Ethical, Legal and Social Implications Research, to be called CEERs, to fund research teams trying to integrate basic genomics, clinical and health policy research, ethics, law, the humanities, and other areas.
The teams will be able to research and respond to "a range of ELSI issues related to emerging genome technologies and the growing proliferation of genomic information," according to the National Institutes of Health's funding announcement.

Specifically, the CEERs will encourage collaborations between diverse groups, make results of their work available to policy makers, and will help train the next generation of ELSI researchers. They will be organized around particular themes, and their research agenda should focus on a single issue or a set of related issues, which ideally will be themes in keeping with NHGRI's large-scale programs.


These programs include the Cancer Genome Atlas; medical sequencing projects; the Human Microbiome Project; the 1000 Genomes Project; the Genes and Environment Initiative, and several others.

"Each of theses projects has raised new high-priority ELSI issues," some of which are already being addressed, NIH said. But the CEER program is aimed "to allow researchers to propose larger-scale, transdisciplinary, and innovative approaches to exploring and addressing them."

Centers that receive funding should have a detailed plan and an effective management strategy, and should promote interactions between researchers across disciplines, such as basic genomics and genetics, clinical and social sciences, law, bioethics, and the humanities.

The centers should also develop new concepts, methods, analyses, and other ways to look at ELSI issues, and should offer ways that could advance controversial issues. They should also try to encompass "the full spectrum of ELSI research," and the policy options and guidelines they offer should incorporate diverse points of view, including communities particularly vulnerable or disproportionately affected by the issues being addressed.

Biogemma to Partner with Roche NimbleGen on Crop Genetics

Genetics-focused agriculture company Biogemma said last week that it will use Roche NimbleGen’s Sequence Capture technology in a research collaboration.

The co-development partnership is aimed at developing new technologies for Biogemma’s crop plant breeding programs. The focus will be on polyploid plant genomes such as wheat and canola.

Using the Sequence Capture complexity reduction technology will help Biogemma target unique genetic variations associated with genes that will be useful to crop breeders, said Roche NimbleGen. The partnership also will employ recent optimizations of the Sequence Capture technology for 454’s GS FLX Titanium chemistry.

Biogemma CEO Pascual Perez said in a statement that the agreement will assist in “development of numerous genetic markers linked to important traits,” and will help Biogemma customers “speed their breeding programs and reduce their time to market, both of which will have a significant impact on agriculture.”

NCI to Provide $90M in Funding for Cancer Genome Atlas Centers

The National Cancer Institute has committed up to $90 million over the next five years to support between four and 10 new centers to advance its Cancer Genome Atlas program.

The institute will spend up to $18 million in 2009 for between two and four Genome Characterization Centers, and between two and six Genome Data Analysis Centers in order to roll out the next phase of the CGA program.

The main aim of the coming phase of the CGA is to provide genome-wide catalogs of genomic alterations for between 20 and 25 types of human cancer. These alterations could then be used to identify and accelerate development of new diagnostic and prognostic markers, new targets for drug interventions, and new cancer prevention and treatment strategies.

The aim for the interactive group of Genome Characterization Centers will be to use genomic and epigenomic analysis technologies for high-resolution genome-wide characterization of cancer-related alterations in the genome.


These centers will use high-throughput technologies to analyze defined sets of cancer biospecimens, to be provided by the Biospecimen Core Resource, to develop four types of data, including raw, processed, segmented, and summary data.

The main goals for the two to six Genome Data Analysis Centers will be to develop two types of analytical pipelines. One goal is to develop and implement bioinformatics systems using available tools, quality control measures, and bioinformatics tools for high-throughput processing and analysis of genome-wide data.

The second aim is to create a “biology-centric” computational pipeline for more advanced analyses to develop models and to identify potential translational directions and outcomes from the CGA data. One type of pipeline is designed to integrate the CGA data via a high-throughput pipeline. The second pipeline will use novel algorithms, models, and other bioinformatics and computational tools to provide biologically relevant results from the CGA data.

In order to fulfill these goals there will be two types of Genome Data Analysis Centers. One will perform data integration, and another type will conduct higher levels of translational genomic analysis. All of these centers will work together to develop strategies for data management, determine the types of analysis to be performed, and optimize the mechanisms for communicating information back to those who participated in the project.

More information about the TCAG funding announcement is available here.

GMU's Human Microbiome Research Center to Run Pyrosequencing Disease Studies

George Mason University is starting a center that will focus on the human microbiome and will conduct genomics studies of microbes that could be involved in diseases, the university said last week.

Funded in part by the National Institutes of Health and the US Department of Defense, the MicroBiome Analysis Center that will attempt to “map the world” of bacteria, viruses, fungi, and protozoa that inhabit humans, and to study their effects on human health.

The MBAC, which will focus on using multitag pyrosequencing, specifically will study microbial imbalances in the gut, mouth, respiratory and urinary tracts, and reproductive systems. Pyrosequencing will allow researchers at the center to “examine, count, and barcode hundreds of thousands of microorganisms per day.”

"This center will allow us to sequence and characterize these microorganisms in order to study their relationship to diseases such as obesity, cancer and irritable bowel syndrome," MBAC Director Patrick Gillevet said in a statement.

Gillevet developed and patented the multitag pyrosequencing technology which will “serve as the backbone of the center’s research efforts,” GMU said.

"Before this technology was developed, we would have been hard-pressed to identify a couple hundred of microbes per sample,” Gillevet said. “Now, we are identifying 50,000 or 60,000 microbes per sample. We can literally do in an afternoon what it took us 10 years to do in the past.”

Gillevet’s team is currently working with others at Rush University Medical Center in Chicago to study the presences of microorganisms in patients with breast cancer, inflammatory bowel disease, cirrhosis of the liver, and HIV.

"Finding the microbes responsible for particular diseases may increase the likelihood of developing new diagnostic tests and treatments for them,” he said.

Integrated DNA Technologies to Use Li-Cor Biosciences' Infrared Dyes in Oligo Production

Custom nucleotide developer Integrated DNA Technologies has struck an agreement with Li-Cor Biosciences that will allow it to manufacture oligos for sale worldwide using Li-Cor’s infrared dyes.

Under the agreement, Coralville, Iowa-based IDT has gained the right to use Li-Cor’s IRDye 700, IRDye 800, and IRDye 800CW. These dyes are designed to be alternatives to fluorophore labeling and to extend sequence read-length and base accuracy for DNA sequencing.

Li-Cor stopped manufacturing its custom IRDye labeled oligos last November, and it now is recommending IDT to supply custom oligos with these infrared dyes, IDT said.

The Scan

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.

Study Reviews Family, Provider Responses to Rapid Whole-Genome Sequencing Follow-up

Investigators identified in the European Journal of Human Genetics variable follow-up practices after rapid whole-genome sequencing.

BMI-Related Variants Show Age-Related Stability in UK Biobank Participants

Researchers followed body mass index variant stability with genomic structural equation modeling and genome-wide association studies of 40- to 72-year olds in PLOS Genetics.

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.