Pursuing the Genome
The NimbleGen array platform was designed to help researchers better understand the genome and the affect of genetics on disease, according to Xinmin Zhang, Ph.D., senior product manager at Roche NimbleGen.
The NimbleGen Sequence Capture Exome technology is focused on the most biologically relevant part of the genome, the exome, capturing only the coding exons that are the most functionally relevant and the best understood 1% of the genome.
The company recently introduced the SeqCap EZ Human Exome v2.0, which allows researchers to capture all RefSeq coding exons and miRNA genes in a single tube. It employs empirical rebalancing, a probe-optimization method, in order to enhance capture uniformity. This process is based on real capture and sequencing data derived from optimization of probe density and coverage for all regions.
Because the platform reduces probe density on regions with high-capture efficiency while increasing it in regions with low-capture efficiency, it provides uniformity leading to detection of over 90% of variants in the exome with a single lane (~3 Gb) of sequencing.
Other recent introductions for the cytogenetics research market include NimbleGen CGX cytogenetic arrays, according to Emily A. Rorem, director for product management. The CGX design is optimized for constitutional chromosome analysis to identify copy-number variation in the genome, which may be associated with recognized and unknown syndromes.
The assay interrogates the entire genome and has a high resolution of coverage over targeted chromosomal regions, including over 200 recognized genetic syndromes, 675 functionally significant genes, and the subtelomeres and pericentromeric regions, she adds. The CGX array portfolio specifically addresses cytogenetic applications and provides scalability with three different array formats to process 3, 6, or 12 samples per slide, she adds.
“In the future, we will expand the capabilities of our long oligonucleotide array platform to include SNP detection, providing accuracy and flexibility,” Dr. Zhang reports. “This technology will aid researchers in validation and follow up on SNPs detected through whole-genome or whole-exome sequencing.”
The company also intends to achieve GMP compliance followed by subsequent submission for clearance of select array products for the cytogenetics market to the FDA, Rorem explains. The SNP program described by Dr. Zhang will also play an important role in the areas of oncology research.
Dr. Zhang emphasizes that bringing new products through the approval process requires new content, which is not always readily available and requires significant research and advanced tools.
“With the recent progress in genomic technologies, most notably in next-generation sequencing, many more genetic and epigenetic markers will be discovered and validated for diagnostic use. We expect that arrays will be an ideal platform to develop tests for this novel content and new markers.
“For many genomic studies, researchers are discovery-driven and not necessarily hypothesis-driven. Therefore, the focus and end results of the research do not always establish the link between diseases and genes. This doesn’t necessarily reflect on the technology as long as arrays continue to deliver accurate and comprehensive data. The key bottleneck to this issue is in the experimental design and data analysis.”