Targeted Sequence Capture
Despite NGS advances, notes Michelle Lyles, Ph.D., vp, marketing and sales, febit, “it still takes weeks to sequence a typical mammalian-sized genome at an acceptable depth of coverage for most applications (such as rare mutation discovery).”
Certain high-value genome regions are associated with certain disease states, phenotypic traits, or responses to drug treatment or other environmental stimuli. Dr. Lyles explains that targeted resequencing of genomes can identify variants faster and at a much lower cost than whole-genome sequencing.
“What febit’s technology, called HybSelect, can do is find the needle in the haystack,” maintains Dr. Lyles. “Essentially, HybSelect focuses your sequencing efforts on the areas you want to sequence. febit integrates microfluidics and temperature control with classic microarrays into an instrument called the Geniom RT Analyzer. The instrument, with our bioinformatics approach for capture probe design, allows capture of regions of interest on Geniom Biochips.”
Genomic hot-spots ranging between tens and thousands of kilobases are targets for HybSelect. “You can load your sequencing libraries, hybridize them to capture probes on the Biochip, and conduct wash steps all in an automated fashion and all on a single instrument,” Dr. Lyles notes.
“HybSelect automates capture by hybridization and elution of the DNA of interest. Our customers are looking for capture-enrichment technologies for particular applications, and we are aligning our goals to address that.”
Applied Biosystems’ Dr. Rhodes says the company aligns for NGS expansion by providing end-to-end solutions for each application, with the goal of making sure that the entire process—sample preparation, library construction, sequencing reactions, and bioinformatics—are “as simple as possible.”
At the CHI meeting, Dr. Rhodes will present the latest data from the SOLiD system, emphasizing how the product enables researchers to use a single system to carry out systems biology experiments. “I’ll show examples in which genome sequencing data and transcriptomics data are combined,” he says. “I’ll also highlight some of the new analysis tools available as well as the results obtained with them.”
The biggest challenge, according to Dr. Rhodes, is bioinformatics. “The other parts of the NGS process are improving at such a pace that our users have found the bioinformatics hard to keep up with,” he explains. “To alleviate this, we make sure analysis is simple to execute and, as much as possible, in a preconfigured pipeline so that the user needs minimal interaction.”
“Many people bought machines and produced data; now analyzing that data is the issue,” adds Martin Seifert, Ph.D., GM Genomatix. “We start where hardware ends—we bring all the data analysis into one place and give it context.”
Dr. Seifert’s presentation will focus on live data analysis to show Genomatix’ core strength. “The large amounts of data derived from NGS projects make efficient data-mining strategies necessary if we are to keep pace with the platform data flow,” he explains.
“I’ll show strategies for analyzing epigenetic markers such as methylation. These strategies begin with high-efficiency mapping of raw sequence tags, rapid clustering and peak finding, and data integration into an up-to-date genome annotation database for downstream analysis. I’ll show seamless mining of enriched regions for epigenetic markers in correlation with RNA-seq data.”