>> My name is Russ Altman, I am on the faculty
at Stanford in a number of
departments, including Bio-engineering and Genetics. they
pay me, and then I have an appointment in medicine and in
computer science and I live nearby at Stanford, from New York originally.
>> That's great. And you are one of
the creators, the creator, I guess of Pharmgkb.
>> It's a team.
>> I wrote the original proposal and have continued
to be the principal investigator. It's now in its
13th year. We started back in 2000.
>> Great, and so for somebody who's just seen
Pharmgkb for the first time, what is it all about?
>> So, we are totally excited about the how genetics can influence
your drug response. And, back in 2000 the NIH and others realized
there needed to be a centralized repository to gather all that information
together. So, the mission of Pharmgkb, simply put, is to understand all
human genetic variation that, that impacts drug response and to
catalog it to make it available to researchers, and eventually practitioners.
So that they can use it in their work. And it's
a one stop shop for the genetic influences on drug response.
>> That sounds like a mountain of information.
>> We have, we do, we do this in two ways. We have human curators
who are experts in pharmacogenomics. And they read
the literature literally every week as the journals
come out. They scan them looking for genes and drugs. And
their relationships being discussed. And then put them on a queue
for human curation. This has become difficult, and so the second
effort in the lab are software tools to do this. So
we do a lot of natural language processing, data mining and
stuff like that, to try to help put good articles in
front of the curators so that they can be more efficient.
We do still want humans in the loop, because this is
sufficiently tricky and the end goal being it might
actually affect patients. So we're not ready to close
the loop and just have computers doing it all.
So there's always a human in the loop so far.
>> Well, who's the intended audience for this? Is this sort
of opened up mainly to clinicians or science people or anyone?
>> It's a great question, and that
has evolved. For the first five, seven years
of the database. It was specifically just
for pharmacogenetic researchers. To let them know what
was known and what was not known. Really, so
that it could pick the problems to work on.
And not reinvent a wheel, or be unaware of
some important discoveries that have been made. With the success
of the field, however, it has become, increasingly apparent
that some of this stuff is ready to roll out
in clinical practice. And so, we are now, involved
in consortia. Where we're actually writing clinical practice guidelines for,
clinicians, to actually use pharmacogenomics in
practice. And, and that's probably where
we'll stop. We'll probably go all the way from the raw data.
>> Mm hm.
>> all the way up to the clinical advice that you
would give to a physician who's making a decision about drug prescribing.
>> Wow.
>> And that's really exciting because that's how
you actually impact patients. And that's why we do
this. We do this because we all believed that
the genome was going to be important for health.
And your response to drugs turns out to be one of the key,
early uses of the genome that we'll be able to benefit patients with.
>> So if you were an individual, just a layperson,
who had personal genetic information about, let's say, a gene that
affects the metabolism of a certain drug, you could take
your variation and go Pharmgkb, and what would you find out?
>> So, at Pharmgkb you would find a couple of things.
You would find the entire literature on that drug
gene pair. indexed as to how good was the study,
not how good was the study, but how big
was the study? How compelling were the statistics when they
did the analysis? And you'll find all the individual
papers, but what you'll also find is products that our
team has created to kind of integrate that data. So
these clinical guidelines are one thing that you may find.
>>
>> these require a lot of evidence,
so there is not as many of them as there are things for weaker
evidence. There's about 12 of them. Where
we can really put down clinical advice,
>> Mm-hmm.
>> But our, our curators also put together pathways of drug response to show
what's happening in the liver or what's
happening in the effector cells. That are
affected by all of these genetic variations,
they also write summaries. This gene is
important because and they actually publish these
summaries so that somebody who wants to learn
about a particularly important gene.
>> Mm-hmm.
>> So a, a patient unless they have
scientific background would not find too much. A
physician would find those clinical guidelines and the
supporting evidence. And a researcher would find, well,
a candy land of the raw, the raw published literature and then what we hope are
very useful summaries of it to help them
think about what the next research questions should be.
>> Yeah. It sounds like, a great, amalgamation of
the information that exists, but in a centralized place.
>> We call it a knowledge pyramid. We, in
fact, if you look at the site, Pharmgkb.org. Please visit
it. pharmgkb.org has this knowledge pyramid where we have
the raw data that's published in the literature. And then
we have aggregations of it. And then we have
filtering of it, and then we have the clinical advice
that we give to doctors. And that's really how it
works, you have all this research that eventually Impacts patients.
>> Do you keep of how many entries
you have? Like, how many drug, genetic variation responses?
>> Absolutely. So I do annual reports for the NIH.
>> Okay.
>> And so over the le-, years, we have totally
instrumented the site. We know how many hits every page gets.
>> Wow.
>> We know the most popular pathways
that people look at. The most popular genes.
>> Name one.
>> so people love codeine. And people
[CROSSTALK]
>> Don't they, don't they though.
>> Exactly, it's a pain reliever. People
are very interested in Warfarin. For the
pathways, those are the ones they like, for the genes, they like some of
the genes that are involved, there's a
gene called cyp2d6, terrible name, cytochrome p4502d6,
which is very important for hundreds of drugs. And that's one of our top hits.
>> What other resources would you recommend? I mean,
is, is, do you want Pharmgkb to sort of be
the one stop shop or are there other useful resources that
you would recommend to people sort of in conjunction with this?
>> Absolutely. So couple things. we have
this tab based display format right now. One
of the tabs is Other Resources. And it's very important because what we can do
is since we know the drug or the gene that the user is currently looking
at. We can have super specific links to
other information sources about those drugs, about those
genes, about the diseases that they treat. And so
we have those links and we are always looking for
more links. because this is the beauty of the
world wide web, is you can make these connections. In
addition to that, sometimes a data source is so
valuable that we, with the permission of the people who
are creating it, bring it into the Pharmgkb so
we can more tightly integrate that data with our data
>> Mm-hm.
>> So there's kind of two phases
of the relationship, the, we'll definitely link to
you phase, and then the, we love you so
much that if it's okay with you, we'd like
to bring you in and make you part of
our interface, part of the way we represent information.
And these include Basic biological databases like GenBank, which holds DNA
sequence. There's a very valuable drug resource called Drug Bank, which we link
to. There are the DB Gap, which holds G-WOSS studies, and a
long list of other links that you would find on this site.