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NIH, Max Planck Institute for Developmental Biology, 454 Life Sciences, GenomeQuest, RainDance Technologies, dScreen Consortium, Invitrogen, Applied Biosystems, NHGRI, Washington University in St. Louis, North Carolina State University, University of Cali

NIH Awards $190M for Epigenomics Program
The National Institutes of Health this week awarded $18 million in grants to start its Roadmap Epigenomics Program this year. Over the course of five years, NIH plans to fund the program with $190 million in total.
NIH Director Elias Zerhouni said in a statement that the funded Roadmap projects “will provide reference data that the entire community can use to understand epigenetic regulation and how it affects health and disease.”  
The epigenomics program involves a number of NIH institutes, including the National Institute of Environmental Health Sciences; the National Institute on Drug Abuse; the National Institute on Deafness and Other Communication Disorders; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Neurological Disorders and Stroke; and the National Center for Biotechnology Information.
The 2008 awards that NIH announced this week include four research areas: epigenome mapping centers; epigenomics data analysis and coordination; technology development in epigenetics; and the discovery of novel epigenetic marks in mammalian cells.
The Reference Epigenome Mapping Centers will map a variety of human cells that can be used as references for studying disease mechanisms. Four centers will receive awards under the 2008 funding: The Production Sequencing of Reference Human Epigenomes program led by Bradley Bernstein and Alexander Meissner at the Broad Institute/Massachusetts Institute of Technology; the San Diego Epigenome Center, led by Bing Ren, at the Ludwig Institute for Cancer Research; the Integrated Epigenetic Maps of Human Embryonic and Adult Cells program, led by Joseph Costello of the University of California, San Francisco, and Marco Marra of the British Columbia Cancer Agency; and the Northwest Reference Epigenome Mapping Center led by John Stamatoyannopoulos, at the University of Washington.
The Epigenomics Data Analysis and Coordination Center will integrate the data and information from the programs by providing informatics and analysis. It will be headed by Aleksandar Milosavljevic and Arthur Beaudet at Baylor College of Medicine.
The Technology Development in Epigenetics awards will fund projects that may transform future epigenomics research. The researchers receiving these grants include Mark Bedford of the University of Texas MD Anderson Cancer Center; Or Gozani of Stanford University; Harold Craighead and Paul Soloway at Cornell University; Howard Hang of Rockefeller University; Steven Henikoff at the Fred Hutchinson Cancer Research Center; Shohei Koide of the University of Chicago; Rihe Liu of the University of North Carolina at Chapel Hill; Robi Mitra at Washington University, St. Louis; Huidong Shi of the University of Missouri-Columbia; Kun Zhang at the University of California, San Diego; Alan Jackson of the University of Arkansas for Medical Sciences; and Sean Taverna at Johns Hopkins University.
The Discovery of Novel Epigenetic Marks awards will fund scientists trying to determine whether genome-wide regulating factors exist and if they may be specific to certain types of cells. Scientists receiving funds under this program include Xian Chen and Brian Strahl at the University of North Carolina at Chapel Hill; Xiaodong Cheng at Emory University; Patrick Grant of the University of Virginia; Richard Katz at the Institute for Cancer Research; Marjorie Oettinger at Massachusetts General Hospital; Alexi Tulin and Kenneth S. Zaret of the Institute for Cancer Research; Peter Warburton at Mount Sinai School of Medicine at New York University; and Yingming Zhao at the University of Texas Southwestern Medical Center at Dallas.
More information about the program is available here.

Researchers Complete First Arabidopsis Sequences in 1001 Genomes Project
Researchers are undertaking a project to sequence 1,001 different genomes of the model organism Arabidopsis thaliana, or thale cress, the Max Planck Institute for Developmental Biology announced this week.
MPI Director Detlef Weigel and his colleagues reported data from the first step of the project online last week in Genome Research, illustrating that they could sequence the Arabidopsis genome using short reads generated with an Illumina Genome Analyzer.
Thale cress is found throughout the Northern Hemisphere, but only recently have scientists started to understand how genetically diverse the organism is. For the 1001 Genomes Project, researchers intend to sequence a total of 1,001 A. thaliana genomes and look at how genetic differences between strains correlate with factors such as plant growth speed, branching, and disease resistance.
So far researchers have sequenced and compared the genomes of two A. thaliana strains — one from Ireland and one from Japan — and found them to be surprisingly distinct from one another, differing by several percent of their sequence. The researchers hope to understand this sort of variation within a broader species context, comparing 1,001 strains from around the world.
The team plans to sequence the genomes of 80 thale cress strains by January 2009 and 1,001 strains over the next two years.

454 to Offer GenomeQuest Informatics Service with GS FLX System
Roche’s 454 Life Sciences has inked a co-marketing deal with GenomeQuest, whereby GenomeQuest will offer its On-Demand Informatics Service to users of 454’s Genome Sequencer FLX.
According to a statement from 454, GenomeQuest’s high-throughput annotation and data-management tools enable rapid characterization of sequences generated by the GS FLX system. The co-marketing pact was signed following a pilot study to evaluate the accuracy and scalability of GenomeQuest’s algorithms and informatics platform, said 454.
“When GenomeQuest first proposed to us the ability to computationally screen all of the sequences of an instrument run in one pass to provide annotated reads to our customers, we were hopeful, but cautious,” Edward Szekeres, manager of production informatics for 454, said in a statement. “Ultimately, they exceeded our expectations for each test case.”

RainDance Joins French HTS Screening Consortium
Microfluidics company RainDance Technologies said this week that it has joined a French consortium to develop a microfluidic system for use in quantitative high-throughput screening of potential drug compounds.
In addition to the Lexington-Mass.-based company, the dScreen Consortium includes the drug-maker Sanofi-Aventis and the Institute for Science and Supramolecular Engineering at Louis Pasteur University of Strasbourg. The consortium was founded with assistance from the Alsace BioValley cluster.
One of the consortium’s goals is to develop a microfluidic system for quantitative high-throughput screening of bio-active compounds using purified targets and cell-based assays. Such a system would enable researchers to gauge dose-response curves for compounds in a chemical library.
Another effort will be to develop a new system for storing compounds in which each compound will be stored in droplets using a microfluidic device.
Separately, RainDance said this week that it plans to make its first product, a sequence enrichment process for targeted genome sequencing, available to early-access partner “soon” and to launch the product commercially during the first quarter of 2009.

Invitrogen Nails Down $2.5B in Financing for ABI Deal
Invitrogen said last week that it has secured the financing lines it will need to complete its acquisition of Applied Biosystems, a deal valued at around $6.7 billion in cash and stock.
Funding for the two loans, which will total around $2.65 billion, came from two groups of lenders. One loan that includes $1.4 billion and a revolving credit facility for $250 million was committed by a group of 30 bank lenders. A second loan of $1 billion will come from 250 committed lenders.
“The syndication contains a well-diversified base of domestic and international investors, who see the value in the significant cash flow and future potential of the combined company,” Invitrogen CFO David Hoffmeister said in a statement.
The company expects the merger to close in November, once the nod comes from shareholders and the European Commission. The deal has already cleared US antitrust hurdles.

NHGRI to Back Data Management for 1000 Genomes Project in 2009-2010
The National Human Genome Research Institute plans to fund two research programs over the next two years supporting researchers who will create ways of handling and analyzing data from the 1000 Genomes Project.
The 1000 Genomes Project, a collaboration between NHGRI, the Beijing Genomics Institute Shenzhen, and the Wellcome Trust Sanger Institute, is focused on sequencing the genomes of between 1,200 and 1,500 people worldwide. That program should produce around 20 terabases of sequence data, according to NHGRI.
NHGRI said last week that it plans to issue a request for applications this fall to fund up to six awards in fiscal 2009 for data processing research. This program will seek applicants who will continue to develop, evaluate, and implement methods for producing data types; monitor and integrate data; and develop tools and processes needed to produce the final dataset for the project.
The work will be conducted under the 1000 Genome’s international collaborative consortium.
Data processing pipelines are already are being set up to use the sequence data, and these will need to be improved and monitored, and new processing steps will need to be added, NHGRI said. The complete dataset will need to be characterized in several ways, and will need to have several types of global analyses, and tools will be needed that can allow the research community to use the data, according to NHGRI.
The second RFA for analyzing the complete dataset will fund around ten awards in fiscal year 2010. The researchers may characterize and analyze allele frequency distribution and signals of natural election. The funding will go to develop tools that will be needed to work with data and apply them to other studies, such as genome-wide association studies. This RFA will be released this fall in order to allow applicants sufficient time to “develop meaningful collaborations and responsive projects.”
Neither of these programs will support using the 1000 Genomes data for the analysis of genetics of specific human diseases or other phenotypes.

Max-Planck, WashU Researchers Sequence Genome of Dead Beetle-Scouring Nematode
Researchers from the Max-Planck Institute for Developmental Biology and the Genome Sequencing Center at Washington University in St. Louis have sequenced the draft genome of Pristionchus pacificus, a nematode that feeds on the fungi and bacteria found on dead beetles.
The work, published online last week in Nature Genetics, suggests that the tiny worm’s genome contains an unexpectedly large and diverse set of genes — including those involved in breaking down harmful substances and surviving in harsh environments. And because P. pacificus’ lifestyle appears to be an example of pre-parasitism, the findings are expected to provide new insights into the genetics of host-parasite interactions and the evolution of parasitism.
For this paper, researchers focused on a California strain of P. pacificus, a “necromenic” nematode that lives on an oriental beetle species in the US and Japan, feasting on the fungi, bacteria, and other miniscule creatures that colonize the beetles after they die. The worms invade beetles during their non-feeding, resting stage — which resembles the infective life stage of parasitic nematodes — and then continue developing after the beetles die.
The current draft genome — obtained by sequencing the 169 megabase genome of a California strain of P. pacificus to nine-fold coverage using whole-genome shotgun sequencing — represents roughly 84 percent of the worm’s complete genome. The researchers also sequenced three other Pristionchus genomes, including that of a Washington strain of P. pacificus, to various coverage levels, using the California strain as a reference genome.
Based on their subsequent analysis, the researchers predicted that the P. pacificus contains more than 23,500 protein-coding genes — more than the free-living nematode C. elegans, which has about 20,000 protein-coding genes, and the human parasite Brugia malayi, which has roughly 12,000 protein-coding genes.
The team found that P. pacificus had gene duplications in regions of the genome that could help it survive in and on the beetle. The genome also contained genes coding for detoxification and degradation enzymes that likely help the worm thrive on dead beetles.
In the future, the team predicts that an improved understanding of the genetics behind P. pacificus’ development, behavior, and ecology will lead to a clearer view of parasitism in general.

Sequence of Nematode Genome Sheds Light on Evolution of Plant Parasitism
Researchers have sequenced the genome of the northern root-knot nematode, Meloidogyne hapla, a soil worm that parasitizes the roots of plants, including many crop plants.
The work, which appears online this week in the Proceedings of the National Academies of Science, suggests that the M. hapla genome, the smallest multicellular animal genome sequenced to date, has been pruned down in many areas compared to other nematode genomes, but has expanded in other regions — particularly those containing parasitism-related genes. And, researchers say, the new genome sequence may open the door to a more complete understanding of the nature and evolution of plant parasitism.
For the paper, researchers from North Carolina State University, the University of California Davis, the Department of Energy’s Joint Genome Institute, and the University of California sequenced the roughly 54 million base pairs of the M. hapla genome to about ten times coverage using whole-genome shotgun sequencing with ABI 3730 and MegaBase sequencers and assembled it using Arachne software from the Broad Institute.
Their subsequent analysis predicted that the small, but dense, M. hapla genome contains 14,420 protein-coding genes — thousands fewer genes than the C. elegans genome. Several gene families, including those for the G protein-coupled receptor, nuclear steroid hormone receptor, and collagen genes, were also sharply abbreviated compared to those in C. elegans.
While nearly half of the M. hapla genes with known functions shared high similarities with genes from C. elegans, others — which appear to have been acquired, in part, through horizontal gene transfer — resembled genes in parasitic bacteria and fungi.
In the future, the authors noted, by combining sequence information with whole-genome transcriptome profiling and other types of analysis, it should be possible to delve even deeper into M. hapla’s pathogenicity, development, and evolution. Such information may help researchers understand how the worm infects plants — and, eventually, could provide new targets for anti-nematode therapeutics.

Roche Taps Integrated DNA Technologies for 454 GS FLX Fusion Primers
The nucleic acid design and supply company Integrated DNA Technologies will provide Roche Diagnostics with fusion primers for some 454 sequencing applications, Roche said last week.
The exclusive agreement calls for IDT to design, synthesize, and purify the primers for use with the 454 Genome Sequencer FLX system.
The applications that the IDT primers will suit include ultra-deep amplicon sequencing for detecting low-frequency mutations in disease-linked genes, and identification and quantification of common and rare variants in a population.
The IDT fusion primer design software uses a gene-specific database number or a reference sequence to develop 454 FusionPrimers for targeted DNA regions, including individual exons or all the exons from one or more genes, the company said.
“The software takes into account performance metrics of the entire fusion primer rather than simply adding 454 Life Sciences’ universal adaptor sequence to an otherwise standard PCR primer,” IDT said.
"By shifting the task of primer design to IDT's online tool, researchers can now focus their efforts on making discoveries,” 454 Life Sciences’ CEO Chris McLeod said in a statement.

Synamatix, GeneWorks Partner on Next-Gen Sequencing, Analysis Services
Synamatix, a bioinformatics firm based in Kuala Lumpur, Malaysia, said last week that it is partnering with Australian genomic services shop GeneWorks to provide next-generation sequencing services and bioinformatics support to customers in Asia and Australia.
Under the terms of the partnership, GeneWorks will provide sequencing services on the Illumina Genome Analyzer platform, while Synamatix will provide bioinformatics analysis using its SynaWorks platform, a suite of tools targeted at analyzing data from the Illumina and Roche/454 sequencing instruments.
The companies said that the first project they are working on is “an initiative covering the de novo sequencing of microbial organisms,” but did not disclose further details.
The companies said that they expect their combined services to appeal to small and medium-sized research institutions “by enabling scientists to enhance and accelerate their research without being limited by a lack of bioinformatics resources or capabilities.”

Clinical Data Raises $25M in Private Placement
Clinical Data has raised $25 million through the private placement of 1,514,922 shares of newly issued common stock to affiliates of Randal Kirk, chairman of the Newton, Mass.-based firm’s board of directors.
Clinical Data said that the purchase price was $16.44 per share, which was its closing price on Sept. 26, plus $.0625 per share, and warrants to purchase an additional 757,461 shares of common stock at $16.44 per share.
The publicly traded firm said that it would use the funds for general working capital purposes.
Cogenics, a unit of Clinical Data, installed a 454 GS FLX sequencer at its Genome Express sequencing service facility in France last year (see In Sequence 4/3/2007).

Arcxis, Roche Collaborate on Molecular Diagnostics Sample Prep
Arcxis Biotechnologies said last week that it will collaborate with Roche Molecular Systems, a business area of Roche Diagnostics, on sample-preparation technology for molecular diagnostics.
Under the collaboration, Arcxis will use its proprietary total RNA and genomic DNA isolation and concentration technology with PCR and RT-PCR-based diagnostic tests. The company expects that its methods for preparing blood and tissue will produce “significant performance benefits” for PCR-based tests.
Arcxis said the partnership offers an opportunity to apply its technologies to infectious disease and cancer detection tests.
“Many companies, large and small, have struggled to purify nucleic acids for molecular diagnostic tests. We believe that the application of our technology will extend the dynamic range of assays,” Jay West, Arcxis’ chief technology officer, said in a statement.

US Genomics Lands $4.5M Equity Investment from BD for Pathogen Detection Tech
US Genomics said last week that Becton Dickinson has taken a $4.5 million equity investment in the firm, and the two companies will collaborate to develop a molecular diagnostic test for infectious disease.
Under the collaboration, the companies will develop US Genomics’ DirectLinear Analysis technology for use in a test that will detect a range of pathogens based on genotype.
A test based on the DLA technology, which integrates labeling, microfluidics, and optics, could identify a pathogen and test for virulence and drug resistance in a sample within hours, as opposed to several days, US Genomics said.
The test could help doctors predict what drugs a pathogen may be resistant to, and which drugs might make the most effective treatment, the company added.
US Genomics said that it has so far invested more than $50 million in developing the DLA technology, with support from venture funding, the US Department of Homeland Security, the National Science Foundation, and the Defense Advanced Research Projects Agency.
US Genomics’ CEO, John Canepa, said in a statement that DLA’s uses include bio-security, bio-surveillance, and environmental and food safety testing.

Li-Cor Biosciences Offers $1.75M in Matching Funds for Undergrad Genomics
Li-Cor Biosciences said last week that it is awarding $1.75 million in grants under its Genomics Education Matching Fund, which supports undergraduate genomics education.
The Lincoln, Neb.-based company said that the program provides 60 percent of the funding for qualifying institutions that acquire its DNA sequencing systems for use by undergraduate students.
Students with hands-on DNA sequencing experience “have a distinct advantage when they seek jobs and admission to post-graduate programs,” Jackie Potts, coordinator for the GEMF program, said in a statement.
The company said that more than 200 undergraduate programs currently are involved in the matching fund program.
The package the company is making available through the grant program includes its sequencer, training, software, and a one-year on-site warranty.

The Scan

Study Links Genetic Risk for ADHD With Alzheimer's Disease

A higher polygenic risk score for attention-deficit/hyperactivity disorder is also linked to cognitive decline and Alzheimer's disease, a new study in Molecular Psychiatry finds.

Study Offers Insights Into Role of Structural Variants in Cancer

A new study in Nature using cell lines shows that structural variants can enable oncogene activation.

Computer Model Uses Genetics, Health Data to Predict Mental Disorders

A new model in JAMA Psychiatry finds combining genetic and health record data can predict a mental disorder diagnosis before one is made clinically.

Study Tracks Off-Target Gene Edits Linked to Epigenetic Features

Using machine learning, researchers characterize in BMC Genomics the potential off-target effects of 19 computed or experimentally determined epigenetic features during CRISPR-Cas9 editing.