Validating TruGene on MiSeq
On November 2, 2011, Siemens Healthcare Diagnostics and Illumina announced that they entered into a partnership aimed at setting new standards in the use of next-generation sequencing for the rapid, accurate identification of patients’ infectious disease states and potential treatment paths.
Siemens and Illumina will initially work on making Siemens’ TruGene® HIV-1 Genotyping Assay, one of the first FDA-approved HIV-1 DNA sequencing-based tests, compatible with Illumina’s MiSeq analyzer.
“We had an FDA-cleared product on the market, TruGene, based on a slab gel sequencing technology, for eight years,” said Trevor Hawkins, Ph.D., head of next-generation diagnostics for Siemens’ Healthcare Diagnostics. “We looked at it and said this is a great starting point for Siemens to begin to understand how these next-generation sequencing devices could be used in real clinical settings. We have a large global TruGene community developing a lot of datasets and understanding of how to use sequencing in the clinic.”
He further explained that Siemens “got into this as we wanted to see what it would take to understand how to standardize methodologies, workflow, and IT/automation and answer all the questions on the table, including those related to chemistries and how data management would be handled.
“The key things we have been doing over the last couple of months include validation of results run on a standard TruGene platform versus those run with the MiSeq system and analyzing any differences in the data.” There is so much data that one of the key questions Dr. Hawkins seeks to answer is at what depth and sensitivity levels do you start to use the data in a clinical setting.
Dr. Hawkins also noted that Siemens has “been looking at cloud-based IT solutions; all these devices are cloud-enabled, so what will the impact be of cloud-based systems in the next 10 years? How will the TruGene community use cloud-based tools?”
Siemens is working on analyzing HIV sequences from the traditional platform for its HIV tests and analyzing output for known drug resistance. “The way in which next-gen systems work is inherently different from Sanger-based sequencing,” Dr. Hawkins pointed out. “The issues at hand are ones of using new chemistries and then validating that you are getting the same quality of results over large datasets.
“That is the work that has to go on: sequencing the same sample multiple times using the old technology and the new technology to ensure you are arriving at the same end-point answer at the same or better qualities with the new approaches.”
Siemens plans to go to the FDA this year with its next-gen sequencer-based tests. “Our programs in HIV are going as expected, and we are now looking at what potential assays could be our next challenge in taking next-gen sequencing to the clinic,” Dr. Hawkins stated. He anticipates that the FDA will be a partner in understanding how the devices will be used.
“Next-gen sequencers will change the way in which we interact with healthcare,” he asserted. “Everything we have seen before is going to change over the next five years because of these devices. We formed the partnership because Siemens wanted to be at the table talking to the customers, the community, and the FDA to see a real-world example of a widely used test.”
Investigators studying the use of next-gen sequencing in identifying patients, for example, at risk for breast cancer say that the cost savings in applying such technologies will allow the application of genetic testing to a wider range of individuals than is the current standard.
They also say as more next-generation sequencing technologies become available for genetic testing, results on sensitivity and specificity should be made freely accessible to those who order the test. Hopefully, they say, comparisons of various technologies will also become available.