By Monica Heger
A new lab has opened at Imperial College London with a focus on developing sequencing-based diagnostics for cardiomyopathies, leukemias, and infectious diseases, among others.
The new facility, called the Molecular Pathology Laboratories, is run by the Imperial Molecular Pathology Group, a union between medical faculty at the college and Imperial Healthcare NHS Trust hospitals.
"Operating within that framework, we have a very large patient population for which we want to develop molecular diagnostic testing, using next-generation sequencing," said Tim Aitman, chair of the Molecular Pathology Group.
The lab, which officially launched this week on the college's Hammersmith campus, is equipped with both an Illumina HiSeq 2000 and a Roche 454 GS Junior instrument. Additionally, Imperial College's Brompton campus has Life Technologies' SOLiD, and a Genome Analyzer and an additional HiSeq are available at the MRC Clinical Sciences Center Core Genomics laboratory at Hammersmith.
Aitman said the group's core areas of interest are in cardiovascular and metabolic diseases, leukemias, and infectious diseases. Specifically, familial hypercholesterolemia and cardiac arrhythmia are the "two front- running areas," he said.
While in some cases, the sequencing-based tests may eventually replace current diagnostics tests, Aitman said that is not the short-term aim, which is to "use the technology to broaden the scope of genetic testing into new areas such as identifying Mendelian subtypes of common diseases where genetic diagnosis is currently challenging, and track bacterial infection."
Imperial College also has two accredited laboratories — the Molecular Hematology lab, which specializes in chronic myeloid leukemia, and the Molecular Virology laboratory, which specializes in HIV.
Initially, diagnostic tests developed on next-gen sequencers will be validated with Sanger sequencing in the accredited labs, said Aitman. Ultimately though, one of the next-gen sequencing platforms will become part of the accredited pipeline, although not in the immediate future.
Aitman said that the diagnostic tests would primarily be based on sequencing gene panels and that "whole-exome and whole-genome sequencing is of more value in a research context." He added, however, that whole-genome or exome sequencing could be useful in "cases that are difficult to diagnose."
He said that the lab has not yet settled on specific technologies for the different tests it is developing, and that the final choice would depend on a variety of factors including the required depth of sequencing and the turnaround time needed.
Aitman declined to divulge how far along the lab is in developing its tests, but said it plans to roll out the first ones, likely to be cardiovascular, to clinicians within Imperial College over the next one to two years. The team has been using the tests internally among a small number of investigators and they have proven successful so far, he said.
Additionally, the group plans to use whole-genome sequencing of bacterial and viral isolates to track infection, although this project is still at a very early stage, Aitman said.
For that project, the team plans to sequence bacterial genomes from multiple individuals or sites within a community, such as a hospital, and see if they can piece together how each individual bacterial isolate is spreading by clustering the isolates according to sequence similarity.
"Bacterial genome sequencing is now the standard for these types of projects," Aitman said. "Serotyping and genotyping methods that have been used to categorize sub-isolates of bacterial infections have now been shown to be less effective than whole bacterial genome sequencing."
Finally, the group is interested in coupling next-gen sequencing with clinical trials, although it is not currently involved in such a project.
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