Good afternoon.
This is Peter Cooper from the customer service division of NCBI . Today's webinar is on Medical
Genetics Summaries on the NCBI Boolshelf.
With me as Adrianna Malheiro who is a genetic counselor NCBI and she will be talking you
about the Medical Genetics Summaries.
If you have a question during the webinar, write it into the question pod.
The answers are going to be available after the webinar, linked to our webinars page.
In their will be the slide set and materials directly as well.
I'm goint to pass this over to Adrianna.
Thank you, Peter.
Welcome to the NCBI minute!
It is with great pleasure that I am introducing you to your new best friend for actionable
pharmacogenetic information, the Medical Genetics Summaries
In the clinic, a physician, genetic counselor, nurse or pharmacist may want to efficiently
access authoritative information about genetic testing to guide therapeutic decision making.
This is where the MGS come in.
You can use them to find pharmacogenomic information about drug efficacy, dosing, or adverse event
risk.
The Medical Genetics Summaries were created by NCBI to bring a clinician a trustworthy,
quickly digestible resource that summarizes the latest pharmacogenomic information in
an actionable format.
Each chapter is written in house by a doctor with pharmacology background, edited in-house
by clinical geneticists, and then sent for outside editing by an impressive list of expert
reviewers – they are all acknowledged in each chapter so you can see whose input contributed
to the summary.
Summaries are updated regularly.
You can access Medical Genetics Summaries for free from the Bookshelf which is where
NCBI stores its free books like GeneReviews that you may be familiar with.
You can use it to find the over 300 pharmacogenetic tests currently in GTR.
And access information in MedGen.
These clinical genetics resources at NCBI all link to each other.
The main page lists all summaries and you can expand to see links to specific sections
of each chapter for quick access to the specific information you need.
There is a search box where you can look for summaries by drug or gene.
The MGS is a collection of currently 37 chapters or summaries and this number is growing.
Each summary has the same format.
Each chapter or summary starts with a concise introduction that describes the drug and its
metabolism, how the genetic variation influences the drug response, and the take-home messages
from FDA and other authoritative sources.
The introduction also shows dosing guidelines, giving quick access to actionable information.
The Drug, Gene, and Therapeutic recommendations sections go into more detail.
The allele Nomenclature table is your Rosetta stone for variants, to translate common start
alleles, alternate variant names, dbSNP rs identifiers, and HGVS expressions – HGVS
is the standardized nomenclature for human variation.
So, what is in the MGS?
The MGS includes the relevant statement from the FDA drug label.
Professional practice standards from authoritative pharmacogenomic societies like CPIC the Clinical
Pharmacogenetics Implementation Consortium.
It also includes relevant practice guidelines from professional medical societies like the
American College of Medical Genetics and Genomics (ACMG)
It has information from the Pharmacogenomics Knowledgebase, PharmGKB, like potentially
clinically actionable gene-drug associations.
We perform literature searches from PubMed to include the latest papers, reviews, and
guidelines which gives you a curated set of references for a more efficient workflow in
your clinic.
Also included is input and review from experts in the field.
The MGS are accessible from other resources at NCBI.
Here you can see how you can access the summaries from the NIH Genetic Testing Registry or GTR,
which is a free database of orderable clinical and research genetic tests provided by labs
from around the world.
And MedGen, which is a portal to information about phenotypes with a genetic component.
These are the 37 chapters available so far – each chapter is for a drug and the genes
that affect its metabolism or efficiency.
I'll use the summary on Codeine Therapy and CYP2D6 as my example.
Here is the layout of the codeine summary.
It starts with a descriptive introduction of the chapter.
On the right-hand side, there are links to valuable information.
For example, you can see that the GTR search on the drug response and gene are already
set up for you to click on.
When you click on these links you are taken to GTR and a page that lists all relevant
tests.
Deeper in the chapter you'll find more details about genetic testing and how test results
are given, for example as diplotypes of star alleles that need to be translated into a
predicted metabolizer phenotype.
Let's say you ordered a CYP2D6 test.
Or, a patient is coming to you with the results of the test their doctor ordered for them,
and the doctor wants your advice on translating the result into clinical decisions.
Here is what the report may look like.
This report lists a set of markers that were assayed, defined with rs identifiers from
dbSNP.
The genotype is given for each marker.
The genetic result is then described as a diplotype of two star alleles, in this case
'star 1 and star 41.
This laboratory report translates the diplotype into a metabolic phenotype – in this example
'extensive metabolizer'.
Now let's go back to the Medical Genetic Summary.
Here is the translation table for different ways used to report variations by for example
labs and the literature.
Here you can see what the HGVS expression is for a star allele, a piece of information
that is not always easy to find.
The star 41 allele in our example lab report is at the bottom.
This table shows the activity status of each relevant alleles for the CYP2D6 gene: star
1 is a normal function allele and star 41 is a decreased function allele.
These are the Codeine therapy recommendations based on CYP2D6 phenotype, these recommendations
have been adapted from CPIC.
The MGS uses the new published recommended standardized terminology from CPIC.
So, you may notice some discrepancy in the terminology when comparing with other resources.
Here is the star 1 / star 41 diplotype and how it relates to the enzyme activity score.
This result is one normal function allele (star 1) and one decreased function allele
(star 41) so the patient is considered to be a normal metabolizer and dosing should
not be affected; so you can use label-recommended, age or weight specific dosing.
Translating the test results into clinical actions takes some dedication.
The MGS is more efficient than a literature search or wading through an FDA label because
everything you may need is in one place.
The codeine summary displays excerpts from the FDA, CPIC, and the Canadian Pharmacogenetics
Network for drug safety (CPNDS).
In conclusion, a clinician can use MedGen to consider a differential diagnosis, to find
clinical, molecular, and research information about a condition or phenotype along with
links to relevant information.
They can use GTR to find a suitable test for specific genes or diseases.
And they can use the MGS to find: Therapeutic dosing recommendations by phenotype; Enzymatic
activity status of significant alleles; Assignment of likely phenotype based on genotypes
And to translate terms used in published literature with terms used in the laboratory and the
clinic by using the allele nomenclature table.
Here is the url for the Medical Genetics Summaries.
A little tip: a google search will also work.
We are on Twitter, you can follow us for notifications on new summaries being published and updates
to existing summaries.
We are working on getting these summaries indexed in PubMed and expect this to be done
soon.
Thank you for your attention.
I can now take questions.
Thanks Adrianna.
The only real question that is in the pod right now is a question about the genetic
test chart that you showed that had the rs id's in it.
The person wants to know where that came from.
It was definitely in the book but I think this question was more about what would be
the source of something like that?
Yes, the lab report with the CYP2D6 alleles in it.
For the allele nomenclature table we actually do this ourselves.
We just read the literature and we try to find the allele on the dbSNP and for the CYP
enzymes, there is a website that actually gathers all of the information for the CYP
enzymes.
So I don't have the exact URL but that is definitely something that should be at the
end of the summaries and if not, I can send them to you.
Now, if you are referring to the rs numbers for the genetic test reports, this is adapted
from an actual report that comes from a testing laboratory.
For that, I can't answer because I didn't know where they did it.
So a follow-up question for that table, he wants to know if that is not in the medical
genetics summary that allele nomenclature?
The allele nomenclature table is in the medical genetics summaries, yes.
This we do ourselves.
We actually create this table ourselves.
Great.
Thank you.
Another question is about when was the first medical genetics summary done, what date?
It was back in 2012.
So when you first go to the medical genetics summary, the book, we have the dates in there.
So there is the date that a chapter was created and there's a date when the chapter was updated
and all the updates after that will be dated as well.
Thank you, Adriana.
Laura Dean who is the author of this book is commenting on the questions pot and I will
send her answers out to people later on when we get the Q&A document together.
Another question is, for a given drug example can you cross-reference to other targets that
influenced metabolism for example a drug may be metabolized by CYP2D6 and CYP3A4 and so
on.
Yes, so each summary is for a drug and all of the genes or enzymes that affect it's metabolism.
So some of the summaries have discussed more than one gene.
So you can see for instance, Clozapine Therapy discusses CYP2D6 CYP1A2 and CYP3A4.
So we definitely can have discussions of more than one gene for summary.
Are there any examples were the medical genetics summaries disagree with CPIC conclusions.
We display all of the recommendations from FDA and CPIC, the Dutch pharmacology workgroup,
the Canadian group.
So we display all of those.
And sometimes they don't agree with each other.
So it's one of the reasons why we created the summarises was to show that when you are
in a clinic and you need to know what all of the professional societies and what FDA
has to say about it, sometimes some of the medical societies as well like a ACMG or ASCO
they will have recommendations as well.
So we've display all of those that are available.
We don't formulate an opinion here.
We just show and display all of the recommendations from all of the groups that publish on that
drug.
Thank you, Adriana.
I don't see any more questions.
I want to go ahead and close the webinar now and remind you that the slides will be available
on the ftp site that I sent in the chat pod to everybody.
So thank you everybody for coming and we will see you next time.
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