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France's Biogemma to Use NimbleGen Sequence-Capture Arrays in Agbio Research


Biogemma, a Paris-based agricultural biotechnology company, announced last week that it will use Roche NimbleGen's sequence-capture technology in a research collaboration aimed at developing new technologies for its crop-breeding programs.

Biogemma will use recent optimizations of the technology with Roche 454's GS FLX Titanium sequencer to target unique genetic variations associated with genes that will be useful to crop breeders.

While the primary focus of Biogemma's relationship with Roche NimbleGen will be to co-design targeted sequence capture arrays for wheat and rapeseed studies, the French company eventually hopes to bring NimbleGen and 454 tools in house and to use the sequence-capture approach in other studies, according to a Biogemma official.

Nathalie Rivière, head of Biogemma's transcriptomics group, told BioArray News this week that the company decided to adopt the Roche NimbleGen approach to better understand two crops for which it sorely needs more information: wheat and rapeseed.

"These are the two species for which we really lack markers," Rivière said. "One of our shareholders' major needs is to have SNP information for wheat and rapeseed," she said. "These are [the] most complex species we work with because of their polyploidy."

Biogemma was founded in 1997 as a fusion of the biotechnology research endeavors of France's largest plant production groups: Chappes-based cooperative Limagrain; Pau-based cooperative Euralis; Rodez-based seed supplier RAGT; Paris-based agbio firm Sofiprotéal; and Paris-based agbio Unigrains.

Rivière said that Biogemma focuses its research on maize, wheat, rapeseed, and sunflower, and is divided into several research groups. It will be Biogemma's upstream genomics group, comprising a transcriptomics team and bioinformaticists, which will first use the sequence-capture method to study wheat and rapeseed.

"Our mission is to supply deliverables to our shareholders, and that means candidate genes, genetic markers, genetically modified plants, and also knowledge," Rivière said. "For this we have different technologies optimized by complementary R&D teams and we survey and incorporate new technologies to better fit our shareholders' needs and to increase our competitiveness."

Sequence Capture

According to Rivière, Biogemma has in the past procured expression arrays from Affymetrix, NimbleGen, and the University of Arizona, which in 2007 hosted the maize microarray project to develop a whole-genome maize array.

Rivière said Biogemma has also developed an expression array for rapeseed in collaboration with Affymetrix. To date most of the upstream genomics research has been in gene expression, rather than genotyping. The partnership with Roche Nimblegen represents a new commitment to move on to understanding genomic sequences with arrays, she said.

NimbleGen first developed the sequence-capture method together with Baylor College of Medicine researcher Richard Gibbs in 2007 (see BAN 10/16/2007). The method enables customers to produce targeted, sequencing-ready samples in their lab using NimbleGen arrays. Samples are first hybridized to the arrays, which are designed to capture sequences for specific regions of the genome. The captured sequences are then released and ready for subsequent amplification and sequencing, according to the company.

When Roche acquired NimbleGen for $272.5 million in June 2007, officials for the Swiss drug and diagnostic giant said the company would sell the sequence-capture method for use with 454's technology, which they gained through their purchase of 454 earlier that year (see BAN 6/26/2007). Since then, Roche has developed relationships with researchers at Oxford University's Biomedical Research Centre, the Cancer Genomics Group at Barts and The London Medical School, and Baylor — all of which are using the NimbleGen-based sequence-capture method together with the 454 sequencer.


When it comes to Roche's sequence-capture approach, competitors include Agilent Technologies, which last June licensed a method from the Broad Institute that enables researchers to perform target capture in the liquid phase using oligo probes. The Broad's method, called genome partitioning, is based on hybridization to biotinylated baits (see BAN 7/22/2008).

While the method does not use arrays to perform sequence capture, it makes use of Agilent's microarray-fabrication infrastructure to design the probes and construct the oligo libraries. Fred Ernani, Agilent marketing manager for emerging genomic applications, told BioArray News in July that the company believes its genome-partitioning offering "addresses a substantial bottleneck in all [second]-generation-sequencing workflows, and thus will be widely adopted."

Rivière said that Biogemma chose NimbleGen over other approaches because it was "promising and attractive," and because Biogemma was encouraged by similar work it performed on the platform to study maize at Patrick Schnable's lab at the Center for Plant Genomics at Iowa State University.

"For us, this seemed like the most promising approach. Other companies seem to have more experience working mainly with human samples, but human and plant genomes reveal major differences," said Rivière.

Biogemma's first goal will be to co-develop the sequence-capture technology with NimbleGen for wheat and rapeseed studies. The co-development will be done by NimbleGen with the input of Biogemma proprietary sequences and expertise in both bioinformatics and species knowledge. Once that is achieved, Biogemma plans to take NimbleGen's arrays in house.

"We will integrate this into several research programs we have in coming years," Rivière said.

She noted that by having the ability to use sequence capture arrays in its labs, Biogemma could become a useful partner for other international researchers and groups studying crop genetics.

"This is an excellent opportunity to develop partnerships with other international research teams, and to give them access to this technology at Biogemma," she said.

Biogemma researcher Jean-Philippe Pichon told BioArray News that the company has numerous connections to other researchers and groups studying maize, rapeseed, wheat, and sunflower. For instance, Biogemma is working with Catherine Feuillet, a research director at the French National Institute for Agricultural Research, who is a co-director of the Wheat Genome Project.

"By investigating SNPs using this technology, Biogemma will be connected to many other projects and important players in that research field," Pichon said.

'Increased Demand'

According to Roche NimbleGen spokesperson Kary Staples, deals with agbio companies like Biogemma are likely to increase this year as the company seeks to tap into a market that has attracted interest from other array vendors. Affymetrix, Agilent, and Illumina have all stated in recent months that they see sales to agbio customers as a potential growth driver (see BAN 9/23/2008).

"We have definitely seen increased demand from the agbio market and the biotech companies that are driving this market," Staples told BioArray News in an e-mail this week. "Due to this demand and interest, this is one focus for us for 2009," he said. "The Biogemma was the first major collaboration of many that we expect to enter into as we further our penetration into this vast market."

Staples said last week that NimbleGen will launch this month a human exome product for sequence capture on its new 2.1-million-probe HD2 platform. "This product takes the discovery of human genomic variation to an unprecedented level by targeting essentially all human protein-coding exons," Staples said (see BAN 1/6/2009).

Later this year, NimbleGen plans to expand its sequence-capture portfolio to include "products that streamline the path to next-generation sequencing of captured samples and make genomic capture more user friendly with higher-throughput capabilities," Staples said. "These improvements will lower cost per sample and increase sample throughput, thereby greatly facilitating re-sequencing studies," he said.

Biogemma's plan to take NimbleGen tools into its labs later this year is possible because NimbleGen has said it intends to enter the instrument market this year. Staples said last week that NimbleGen plans to launch its MS 200 Microarray Scanner before the end of March, and a higher-resolution MS 250 Microarray Scanner later in the year.

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