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At Institute for Genome Sciences, Long Reads Offer New Path to Finished Genomes

Wednesday, November 6, 2013

The Genomics Resource Center (GRC) at the Institute for Genome Sciences (IGS) has a scientific pedigree and a sample-to-interpretation service commitment that place it in a league of its own. The team operates under a simple mantra: ‘If it can be sequenced, we can do it.’

Both GRC and IGS were founded in 2007 when a high-powered team of investigators formerly at The Institute for Genomic Research (TIGR), led by Claire Fraser, joined the University of Maryland School of Medicine. “The group of faculty and senior staff that came here to start the institute was heavily focused on infectious disease research,” says Luke Tallon, scientific director and founding leader of the GRC. “Our primary goal in joining the medical school was to extend our pathogen genomics expertise into host-pathogen studies and direct clinical genomics applications.”

In addition to its infectious disease and genomics expertise, TIGR was also renowned for its bioinformatics talent — a trait that continues with the group at IGS. The GRC team of 15 staff members is evenly split between wet lab and bioinformatics, and more than half of the institute’s 100-plus employees are bioinformaticians. “One of our strengths is that we go beyond generating efficient, high-quality sequence data. We have teams of analysts and engineers who can assist investigators with downstream analysis and interpretation,” Tallon says.

The GRC has had a mandate to stay on the cutting edge of sequencing technology since its inception. “We are continuously monitoring and evaluating new technologies,” Tallon says. A few years ago, these evaluations led IGS to Pacific Biosciences and its single molecule, real-time (SMRT®) sequencer.

The instrument’s strength in de novo microbial sequencing and other long-read applications made it particularly well-suited to the type of research at IGS. Though there are many factors they consider when choosing a new instrument, an important one is “the relative value of the type of data you’re going to get,” Tallon says. “Small genomes are such a significant part of what we do, and we’re moving more and more into microbial transcriptomes and methylation studies. It’s the only platform that allows us to do all of that really well.”  

Lisa Sadzewicz, administrative director of the facility, notes that anticipated demand is also an important factor in bringing in a new instrument for a core facility. “We are not driven by only one customer or one small group,” she says. “In order to drive down costs, you need to have a wide community from which you can draw projects and samples to fill the capacity of the instrument.”

The PacBio sequencer, which GRC upgraded to the PacBio® RS II last spring, is now a workhorse for generating finished or nearly complete microbial genomes as well as genome-wide methylation data. “We’re now analyzing base modifications and methylation patterns routinely with most of our small genomes,” Tallon says. “We’re also doing metagenomic sequencing using the RS II and exploring ways we can use the long reads to get full-length genes and transcripts out of our metagenome and metatranscriptome samples.”

The team’s attention to optimizing the sequencing workflow has resulted in a high-performance pipeline for finishing genomes. “Prior to PacBio, we couldn’t close genomes without manual finishing efforts,” Tallon says. With SMRT Sequencing, his team is consistently finishing genomes. “Our biggest challenge is getting sufficient high-quality DNA to start a project. If we get that, the genomes are going to close more often than not.”

For more on the GRC’s use of the PacBio system, including details on how the lab optimized its SMRT pipeline, read the complete profile. You can also visit the GRC blog or attend their upcoming applications seminar to hear how the PacBio RS II can advance your research on Thursday, November 7 at 11:00 AM. 

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