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At the Hospital for Sick Children, we're really interested in looking at, like many
people, the utility of using whole genome sequencing in the future for diagnostics and
in clinical care in our pediatric patients. Right now, because of the cost and the turnaround
time, we're exploring other options. Like many of us, we're interested in looking
at whole exome sequencing as that sort of stopgap until whole genome sequencing is easier
to do in the facility, in-house. So in this particular experiments and as part of a larger
research study, we're using whole exome sequencing, employing the technology to rapidly
sequence genes relatively quickly, and in some cases these are known disorders, or in
many cases they're known disorders with several different possible genes and this
is just an efficient way to do this analysis. Of course, if you find a variant in one of
these known genes that's been described before, then perhaps you might have something
that explains the phenotype, whereas if they happen to be gene-negative or you don't
seem to find anything, you can use the whole exome sequencing further to look for other
genes or broaden the phenotype or broaden the spectrum of the mutations that might be
there, and then it becomes more of a gene discovery project. In this particular case,
we've got the patients are undergoing their normal patient of care and in many cases they
would be sent off for gene panel sequencing as part of their clinical care. But then as
part of our research study, we're exploring ways in which we can use whole exome sequencing
instead of that standard panel, in a cost effective way to find the variants that would
be related to the phenotype, in hopes that in the future we'll be able to translate
whole exome sequencing into the clinical space and be able to do those tests in-house rather
than sending them out. So in these tests, as part of the research project, it in no
way influenced or changed patient care or standard of care, it's just a way to evaluate
technologies and see which ones are the most effective and then the most cost effective
to be able to do these tests as we look towards translating into the clinical space in the
future. In the study so far, we've had some really
nice successes in being able to use whole exome sequencing and in comparing to the panel
sequencing that comes back, we've been able to find the same mutations often much faster
than it takes to do the panel sequencing. In many instances, it takes several weeks
or months to come back. Part of the research project, we're able to do exome sequencing
going from DNA right to result in less than a week, and so this has just been a much faster
way to do it and much more cost effective, from our perspective. So in general we've
had really nice concordance between these two tests, and in some instances some individuals
that were negative on a panel test turned out to have a mutation in a different gene
that was in a different disorder but related to the phenotype and it was probably what
was causative. The panel sequencing itself is, you know, any individual clinician would
be ordering a test, they'd have to go through and decide what panel to order. Often they
would be done at the hospital but they could also be done sent away to different companies
or diagnostic centers around the world. For our exome sequencing, everything's done
in-house at the genome center, and so we have six different Proton™ sequencers right now,
mostly using AmpliSeq™ as an enrichment capture. The Proton™ system is obviously extremely quick
to do, and a couple developments, including the AmpliSeq™ enrichment, has really sped up
the productivity and how fast these things can be done, so very easy experiment to do,
very quick, compared to what was done in the past.