Mount Sinai Opens New Genomics Lab with Bank of Ion Torrent Sequencers

By Aaron Krol

September 11, 2014 | The old Roche 454 facility in Branford, Connecticut, will soon be returning to genomic science, as the Icahn Institute at Mount Sinai prepares to set up its second sequencing facility on grounds abandoned by Roche in its shutdown of 454 Life Sciences. Mount Sinai announced today that it has leased the space and purchased an initial bank of eight Ion Proton high throughput sequencers. “These instruments are getting installed, and we’ll be up and running next month,” says Glenn Farrell, Director of Mount Sinai’s Department of Genetics and Genomic Sciences.

Mount Sinai already operates one of the world’s leading hospital-affiliated sequencing centers at the Icahn School of Medicine in New York City. Under the leadership of systems biologist Eric Schadt, the Icahn Institute for Genomics and Multiscale Biology has become known both for tackling research studies into human disease on a grand scale, and for its early adoption of genomic testing as a tool in patient care. An Ion Proton cancer hotspot panel used at the Institute was recently approved by the New York State Department of Health for clinical use in refining cancer treatments, and Mount Sinai pursues more ambitious clinical projects under its research umbrella.

The New York City lab where Dr. Schadt works is now space-limited, Farrell told Bio-IT World, and Mount Sinai is establishing a second genetic testing location that can be more easily scaled up as the hospital system’s sequencing capabilities continue to grow. Branford is also home to a number of genetic specialists, making it an attractive setting for the new center. “With the 454 employees, and the adjacency to Yale University, you’ve got a lot of people with this type of skill set to hire,” says Farrell, adding that Mount Sinai is hiring between 20 and 25 scientists to staff the facility.

Among those hires is Todd Arnold, previously the VP for Research & Development at 454, and now the Managing Director of the new genetic testing lab. His team will be immediately joining a major research project already underway at the Icahn Institute: the Resilience Project, which aims to screen hundreds of thousands of healthy individuals for mutations that are predicted to cause devastating genetic disorders, with the goal of understanding factors that protect against these diseases.

“At the Icahn Institute, we’re known for big data, and we want to look at massive amounts of data points and separate the signal from the noise,” says Farrell. “We’re going to see projects, like the Resilience Project, that need massive high-throughput sample handling and analysis done at this facility.” The lab will also be involved in clinical diagnostics for the Mount Sinai hospital system.

Support for Life Tech 

The Icahn Institute has designed a custom Ion Proton AmpliSeq Panel to use in these large-scale projects, covering 26,000 amplicons across more than 700 genes. As Eric Schadt explained to Bio-IT World by email, this panel, the largest ever designed for the platform, is intended to have as broad a clinical reach as possible. The genetic loci included in the panel cover all known variants linked to rare Mendelian disorders, as well as numerous gene-drug associations. “We then complemented this data by covering all regions harboring variants that are associated with common human diseases across the entire disease spectrum,” Schadt added, “so for example those loci that have been identified and highly replicated in GWAS [genome wide association studies] and WES/WGS [whole exome sequencing/whole genome sequencing] studies.” The resulting panel should be able to meaningfully contribute not only to the Resilience Project, but also to research on complex chronic diseases like cancer, diabetes, heart disease, and neurological disorders. Schadt also writes that the panel will be able to pick up both single-nucleotide variants, and small indels, which have often been a challenge for short-read technologies like the Proton.

The Icahn Institute's new genetic testing lab, under construction at a former site of 454 Life Sciences. Image credit: Mount Sinai

The laboratory’s choice of sequencers offers a much-needed vote of confidence for Life Technologies, the subsidiary of Thermo Fisher Scientific that makes the Ion Proton. Life Tech has struggled lately to keep its market share, as the Ion Proton has failed to catch up with the speed and throughput of Illumina’s HiSeq line of sequencers. The company has heavily promoted a forthcoming P2 semiconductor chip, which is slated to quadruple the throughput of the Proton without requiring users to purchase a whole new instrument; however, that project has been repeatedly delayed since an initial launch date in early 2013 fell through.

Nonetheless, the Icahn Institute, which runs Illumina and PacBio instruments in its New York lab, has determined the Ion Proton is best suited to the very large panels that will be used in the Branford location. “Its low per-sample cost, robustness across sample types, rapid end-to-end data generation, and the breadth of the AmpliSeq targeted custom panel for screening hundreds of targeted genes in a single sequencing assay indicated the platform as a highly efficient system for addressing the large volume and diversity of samples we intend to sequence in our new NGS lab,” said Robert Sebra, the Director of Technology Development at the Icahn School of Medicine, in a press release put out by Thermo Fisher.

In an email to Bio-IT World, Sebra added that the current P1 chip delivers sufficient throughput for the first phase of research at the Branford lab, and that “we do feel confident that the P2 chip will be launched in a timely fashion, and working with Todd Arnold and Dan Sisco [also at the Connecticut lab], we are already deriving a sequencing pipeline that will seamlessly transition to increased throughput by simply expanding the per-chip sample multiplex from P1 to P2, upon that release.”

Mount Sinai has also purchased eight Ion Chef instruments for the new facility. These machines, released earlier this year, automate large portions of the labor-intensive sample preparation process for sequencing. Sebra told Bio-IT World that the Ion Chef workflow “relieves valuable hands-on time and helps prepare chips overnight for next-day sequencing… The introduction of the Ion Chef has really elevated high-throughput performance to underscore the turnaround time offered by the Proton, which is necessary for massive population sequencing projects” like the Resilience Project. 

Genomic Medicine 

The Branford lab — officially the Mount Sinai Genetic Testing Lab-Connecticut — will have a more limited role than Schadt’s New York facility, at least at first. While Schadt regularly performs whole exome and whole genome sequencing in his lab, and has PacBio long-read instruments for assembling the more difficult regions of the genome, Arnold’s lab will be strictly dedicated to targeted sequencing. “What we are striving to do today in Connecticut is to focus on those variants that are actionable, that can impact clinical decision making or reproductive decisions or prophylactic treatment strategies,” says Schadt. “We want to be able to scale up our ability to manage large numbers of samples and run hundreds of thousands of assays a year. This is the scale we need to achieve to meet the demands of our patient population.”

The new bank of eight high-throughput sequencers is a significant investment for Mount Sinai, but by narrowing the focus to areas of the genome known to be medically relevant, the hospital system hopes to see rapid returns in both research and patient care. With a healthcare network that serves hundreds of thousands of patients every year, and ambitions to make genetic testing a routine part of medicine, Mount Sinai is experimenting with ways to quickly expand its sequencing capacity.

Meanwhile, the original genetic testing lab will continue to explore how unbiased knowledge of the entire genome could inform medicine. “We are absolutely preparing for the future that we all envision in which WGS will be prevalent and everyone will be routinely sequenced,” Schadt stresses. “We have built up our informatics capabilities and compute infrastructure, including recruiting top data scientists such as Jeff Hammerbacher [founder of Cloudera and Director of Sage Bionetworks], to enable this to happen.”

There will also be plenty of room for the Connecticut lab to grow as the volume of testing performed in the Mount Sinai system rises. Farrell hints that the Resilience Project will soon be joined by other ambitious sequencing programs covering huge populations.

As 454 Life Sciences, the Branford facility played a central role in the earliest days of next generation sequencing; soon, it will be turned over to the next revolution in genomics, taking an active part in medical practice.