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The annual American Society of Human Genetics (#ASHG22) conference was held October 25 to 29, 2022 in the Los Angeles Convention Center, and the co-hosts discuss the highlights of the conference and notable trends.
Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Dale Yuzuki, Cindy Lawley and Sarantis Chlamydas.
Welcome to the
Proteomics in Proximity podcast, where
your co hosts, Dale Yuzuki, Cindy
Lawley and Sarantis Chlamydis from Olink
Proteomics talk about the intersection of
proteomics with genomics for drug target
discovery, the application of
proteomics to reveal disease
biomarkers, and current trends in using
proteomics to unlock
biological mechanisms. Here we have
your hosts Dale, Cindy, and
Sarantis. Welcome from the trade show floor
of ASHG 2022.
American Society of Human Genetics
in Los Angeles.
And we have all three of us in the
same place and at the same time.
So I have to remember not to look at
you, but to look at
you. But we had a
really and are having an awesome time.
And I want to start with
talking about the workshop that
Olink put on. So who wants to start talking
about the workshop? I'll do it.
Go for it. Yeah. So,
the workshop was an
industry session put on,
by Olink. And we
thought, some people thought we would have
only 50 people. I thought over
there for a presentation by Chris
Wheland, who was
discussing the work that he,
Melissa Miller from Pfizer and
Lyndon Mitnaul from
Regeneron, spearheaded around
bringing these groups together. That
several of these pharma proteomics partners
came out of sequencing
consortium that they brought on another
seven, folks, and then
really built this proteomic data set that
will be public.
What Cindy's talking about is the
UK biobank Plasma Proteome
project. Pharma proteomics. Pharma. I keep
saying Plasma Proteome project, but it's a
Pharma Proteome project.
And Chris, right, was spearheading
it, he organizing it, and here it is.
He's seeking at an industry workshop. So
what did he talk about?
So he had several great
points, but much of it was around this
structure of building a
pQTL data set for a systematic
approach to therapeutic target discovery.
But he also talked, uh, about a couple
of examples within those
data. And what I really liked was where
he looked at... Stratifying
with polygenic risk and then
looking, doing a biomarker study
and using the genetics in a different way
than integrating with looking
at correlations to proteins. Which I
quite like those examples because there are
lots of different ways that genetics can add
value to how you structure your proteomics
studies to improve your power to detect the
relationship between genetics and
disease. So here we had a full
house, right? He's walking
through the goals of the
UKB Pharma Proteome
project. Well done. And then he
had, what,
samples worth of data. Did he talk
really much about the data?
So, he...
like I said, he dug in a little bit
about examples like PCSK9
was an example. I'm trying to
remember if on this talk, he talked about
the ABO blood group. He often uses
that. These are examples that are in that
bioRxiv preprint. And
I'm going to just give away a little
behind the scenes thing I heard last night,
and that was that the Pharma Proteomics
partners were digging the
idea of calling it the UK
OPP, "be down with
the OPP", especially since we're in Los Angeles.
So I thought that was fun, like putting a
Olink in there. But alas,
not to be, not to be
the "Olink Proteomics project"
I did dig
that whole, uh, link to the rap world
sitting here in LA. And when you're talking
about last night, you were actually in a
meeting then? No, we actually had a
celebratory dinner. Oh, how neat. It was
beautiful, really, to see these
people I haven't met in person before
sure. And talked to them. I mean,
that's the advantage of an in person
conference, right? For many of us, it's
like the first time in three years we've
seen each other in person for ASHG,
right? That's right. And actually, since
we're talking about the, ah,
UKB-OPP okay,
PPP. Uh, we actually have,
Evan Mills over here off to
my left. I'm going to drag him in and have
him just say a few words about
he went with me to that dinner. We had
several people from Olink, at that
dinner. And so yeah. Evan, can you just say
hello? And a little bit about your role.
close to the microphone and inside it. Yeah.
there you go. I feel like I'm being let into
the circle of trust here. Thank you so
much, my friends.
Yeah. So this meeting has been incredible.
Uh, my role, I'm the VP of our Global
Strategic Account Team, and
that essentially means
where is Olink going to make the most
impact in the world, trying to make sure
we find those opportunities and work very
closely with those partners. So the
UK Biobank Pharma Proteomics Project
clearly falls into that. And I've had the
privilege of getting to know
and work very closely with the 13
companies. And last night was a bit of a
culmination where everyone sat around the
dinner table, raised the glass.
"Congratulations about the success of the
project". All of the data is actually
going to be coming imminently.
...So it was
really one of those pinch yourself
moments, uh, to be sitting with
I mean there are so many thought leaders in the
space all around one table.
Mark McCarthy. Slavé Petrovski
Chris Whelan. Erin
Smith. Erin Smith. Melissa
Miller. It was just really an amazing
opportunity. So, yeah, it's been a heck
of a meeting. Yeah it has. And
while we're talking about Erin Smith, I
will say Erin Smith's poster, she's at
Takeda. So her poster
here, which used, uh,
proteomics to look at NASH,
won a Reviewer's Choice Award.
I don't know if I'm close enough to the
microphone to actually be recording this,
but just saying that Erin Smith, uh, from
Takeda, her poster that leveraged the
UK Biobank data, won
a Reviewer's Choice Award, and so did Ben
Smith. Sorry, Ben Sun. Erin Smith
and Ben Sun
And of course, the Pharma Proteomics
partners are co-authors on
that. Sun et al paper. Yeah,
I mean, there's a remarkable number. I don't
know if you've described the 19
abstracts and six talks.
We are at a genetics conference and we're a
proteomics company. So I just think this is
a very important future
viewing sign
that uh, the community that's used to
A's, T's, C's and G's are really
opening up to large scale proteomics
and seeing the tremendous impact that
it can have. Sarantis,
as a multi-Omics guy, are you
surprised by this? No, actually
I'm surprised of how many people
and uh, they're talking about the UK
Biobank. I think the
cohort is amazing. We have access and
we have collaborations
with a lot of academic
and pharma companies around these
samples. And the future is here. The future
of genomics is here. Now everybody talks about
the next steps. Proteomics is now
really nice. Genomics. When people
think about genomics, they consider
immediately protomics. We integrate the data
and uh, yeah, they're really
great, great moments to come.
And this question is always what comes
next to discussion for the future?
It was really nice because maybe in
a couple of talks where they
tried discussions and integrations from
Steven Horvath
and really nicely explain that they try and integrate
UK Biobank methylation profiles, and methylation data
and really nicely explain that methylation data
and plasma proteins really correlate to expression of proteins in cells
and really nice correlation between protein levels
and DNA methylation pattern
more than the expression of RNA levels
that seem really nice and
here when you want
to have, um, a better view of
your biomarkers. You have to integrate a
multiomics approach, (different labs
performing) and DNA itself doesn't say
all the truth. Proteins are the
bridge, are the blocks that correlate really
nicely for changes are happening. DNA,
genetics, DNA methylation, epigenetics.
That was a
great, uh, takehome message. From Steve Horvath.
nowadays you're Mr.
Methylation here, right? And at a
genetic conference, there's a lot of
methylation talk, right, in terms of DNA,
RNA, protein and what's regulating the
RNA. I mean, Steven Horvath, he's
talking in the context of UK
biobank, right? And he's giving
this aspiration
wanting methylation data from the UK BioBank
as another -Omic layer.
And then what happens?
All the questions are all
around methylation.
It's like, okay, we know,
we know the - People are excited about that
Pharma Proteome project is going to have
all these great drug targets. We know
it's going to be great biomarkers and all
this great stuff. It's like, okay, well, but
we want something more.
It's the multiomics approach, we're in the era of multiomics, proteomics it's the real bridge
That's the thing... I think that the tool building too.
So I'll also say something else that
um, was just a really exciting
highlight for me was the Allen Award, of
course, a very prestigious ASHG
award that, went to,
Professor Sir Peter Donnelly. He was
knighted in 2019, I
believe. Uh, but he
has been pivotal.
I started at Illumina
during HapMap. So he was a big
leader and proponent for the
approaches that were used in the HapMap
project. And of course, the HapMap project
had like one plate of Caucasian samples,
one plate of Aruba samples,
and half a plate of, ah, each
Han Chinese and Japanese samples.
Right. That was our first swath
at diversity
across, ah, different
ancestral populations.
Uh, and after that, the 1000
Genomes Project, once next generation
sequencing became available. And so all of
that documenting or cataloging
of diversity, he was
pivotal in building out, methods for
analyzing those data. He built
"Structure". Right. So when I was in graduate
school, Jonathan Prichard was one of his
students who built that program.
I think he was a student. I don't think he
was postdoc, I think he was a student. And
this program "Structure" does what?
"Structure"? Actually, I still
see it in most sessions, in at least one
talk in most sessions. Use
of this amazing tool to
essentially take data and
use the data for it to generate, uh,
the number of groups that are represented
by the genetic data. Right. So these are
these dot plots with the different
colors. That's right. Exactly. African in
this dimension. That's right. Asian
in this dimension. Exactly. Yeah.
Beautiful colorful plot
that demonstrates within
this we think there are three
groups or within the data,
letting the data speak for itself rather
than a priori saying. For
me, looking at fish, I was
sampling from eight locations. But if those
eight locations actually only represent
four unique genetic entities,
that says something about how to conserve or
manage fish. But let's go back to Peter
Donnelly. I just want to say what a rock
star he is. And then we can yeah,
just go right ahead. Really want to call out
to this man because he is certainly a
statistical, geneticist statistical analyst.
Right. But
with having that skill, but also
being charismatic and able to
bring people together to
help them see
what's possible with it like being able to
communicate. It just comes down to
communication so often.
And he's such a thought leader here. And so
I was just so excited to see his
and when he told me he was getting an award,
and then I looked up what he was getting an
award, I was just like, he's so humble
and so amazing. The
importance of communicating. Right. The
importance of working with others.
The point I was going to
make before is, as far as the use of
this term Structure, I mean, this
particular program Structure is
that in the UK, people can
say I identify
as sort of I believe my
parentage is Japanese. I have
every reason to believe it. But
genetically it could it be that there
may be some Mongolian in Dale's
background? Who knows? Right.
But then a program like this say
I sign up for "All of U". Right. And
by the way, I went to an
"All of Us" session and it was
fascinating to see that. Yes. Even
though COVID kind of slowed their
enrollment down and slowed the progress
down, they're up and going again.
So I went to joinallofus.org
this morning, and I started the
enrollment. Why, I think they're only
about a half million into their
million sample. Cohorts
and like you mentioned, 50,
right. They're working on getting
great diversity. There was one
talk that talked about engaging, uh,
native American,
uh, native populations,
and they're really emphasizing that. And
there was one particular talk where it was
just how many tribes in
just Alaska, it's like
Well, I mean, there's what is it, how
many ethno linguistic groups in
Africa, right? 54 countries, but like
me of another great
Plenary session, right, where they're
announcing right, genome Centers of
Excellence in Africa. They're getting a
conference in Cape Town in the spring.
Francis Collins we have abstract
submitted to that conference, by the way.
Oh, how cool.
We hope
the emphasis, right, on non
European populations, the emphasis on
diversity, the emphasis on African
genomes I mean, in that one session
they talked about loss of infectivity, they
talked about sickle cell anemia and
just some HIV infections and
some remarkable
disparities in terms
of the number of uh, for example, for
a sickle cell. Right. There are several gene
therapy trials here in the US.
And in Africa? Zero. Ah,
I'd like to double
click back on the all of US program, because
something that I learned here, this
meeting was that it isn't currently set up
in the way that UK Biobank is set
up, uh, with an international
sharing structure, which
I imagine they have good reasons for. But
I think there's a hope that All of
Us will consider creating an international
sharing structure that will enable, if we
build these centers of excellence in Africa,
we want those scientists to be able
to analyze those data or interplay with
those data. Maybe it can't be transferred or
downloaded. But having a federated
sharing environment, having a protected, ah,
sharing environment that allows
insights from those data to then be
transferred, because those investments can
be used globally. Like the, UK Biobank
Project. Sure. I mean, there was
a Tweet, right, that was really popular,
talking about how frequent the UK
Bio bank is popping up. Somebody saying they
felt like every other talk matches the
UK Biobank. It's a great
validation. Cohort right. But
also for
initial findings,
people are still mining those data directly.
I mean, as a grad student, I would imagine
that's a rich data set to have access to and
a lot of sequencing. Right.
I know that you're looking really close to
the new secrets and technologies.
Yeah, well, I mean, Maroon 5,
right? Yeah, we should talk about Maroon 5.
Okay, so it's a gigantic line. I mean, Olink
had our own VIP event. It
was pretty small, right? All
these people lining up to hear Maroon 5
and pictures and stuff like that. But
But why? Why have a
popular band play? Because they
announced two new platforms,
PacBio 15X, the Revio
is 15X the throughput of a Sequel II
The Onso, which is the Omniome
short read platform. You've
got MGI here. You've got
Ultima Genomics here. We've got
Singular Genomics here. We've got Element
biosciences here. All with new instruments,
right. All sort of bringing it to market.
With our own differentiators own
differentiators what do you
think about the cost? Just driving it
down? Just driving it down
now for what does that mean for
Olink? It means great things for
Olink. Why? Because Olink customers
receive the benefit of those lower costs.
Exactly. That ah, they're not held at $6,
a gigabase for
NovaSeq 6000,
as before.
Right.
I have to insert the company line here.
And just say we are not validated currently
on any of these platforms. But we certainly
have collaborations with many of them.
Yes. With
an interest to keep a focus
on how do we continue to drive
down costs in genomics? We see that
correct.
The NovaSeq
X, right? They're announcing $2
a gigabase at the end, toward the end
of 2023, which is fine, and a
new instrument, which they have right here
in the Illumina booth. But you walk over to
MGI, right?
BGI / MGI. They've got a T7,
a dollar-fifty ($1.50)
per gigabase now.
You just say well,
wow, that's pretty remarkable.
That is happening here at this
conference because of all the
different progress with lawsuits
and what have you, Freedom to Operate. But
nonetheless, Ultima
saying we're going to be at $2 a
gigabase come February of next
year. Uh, I went to the Element
talk and it was remarkable,
right, how they're driving down costs and
how they have really high quality.
So one of the interesting things here at
ASHG is science communication,
and of course, with posters, there's some
and it's a remarkable work
being done in lots of places. We have this
thing in our booth, right, with a number of
different posters from the UK biobank.
But I was looking for Cindy's poster and
I couldn't find it because
there are so many people crowded around
it. So Cindy, why don't you tell
us why don't you tell us a little bit
about your poster? Yeah, it was a
bit of a surprise to me, actually, because
there are so many posters. I've not
had a crowd around an
ASHG poster like this
How interesting. In any of the times that I've
presented yourself. That is so cool. It was
really cool. It was cool. So, uh,
things were noticing and someone took a
picture. I thought, would it be great if
someone took a picture? And then there's Dale
taking a picture. I was thinking I should
have worn my other shoes. But anyway,
the
poster is really an
aspirational poster
about the work being done by the UK
Biobank with proteins.
Meaning that, I talk about a
previous proteogenomics project. It's a
little smaller scale on the protein size. So
It's a cohort of cohorts of bringing
together this is the SCALLOP study. Uh, and
then 90 proteins right. And
so I talk about the 90
proteins. How many pQTL discoveries
were made possible by the 30,000 samples,
and then how many of those
from Mendelian Randomization were
able, to have strong
evidence for potential
therapeutic targets. And so if we saw that
same sort of five and a half percent
conversion to potential
therapeutic targets in the UK
BioBank apply that to just
the 1500 proteins that are published
by bioRxiv paper.
That's over 500
potential therapeutic targets. Disease
agnostic across different diseases. So
anything that's going to give pharma,
a more unbiased approach or a
disease agnostic approach to an
evidence to support
consideration of
particular proteins as
targets, I get
excited about that. There
were several people that came,
and I think maybe because of
where it was located, others that were
walking by stopped as well. And so I
got to present it several times, which is
really fun. But an hour and a
half is not enough time for
a
poster session where you
want to see even just
five or ten posters of,
Because there's just
so much space to cover and
you want to have a conversation with each
person presenting it. And so it was
just nice that people took the time
to come.
One particular poster that caught my eye was
one from Takeda, right, that
uses UK Biobank.
Yeah, that's Erin's. Yeah, I think we
mentioned that
when Evan popped his head in, but
yeah, that one that got the Reviewer's
Choice Award
talking about the
potential for these proteins to
suggest something about
the action in Hepatocytes. What are
exosomes? They mentioned in the conclusions,
really, for future,
studies, which is such a hot
topic that people are talking about, but I'm
not seeing a lot of publications yet coming
out. Looking at broad scale
proteomics within the exosome.
I think we have a lot of.
studies that work with small
amounts of protein, Olink
only being able to pick
up protein
signals from a remarkable number of
sample types. And
we're here on the show floor.
There's so much
going on, it's here overhead.
Opening up in fifteen minutes.
The last show
day. Well, any final
thoughts?
Hear from ASHG?
What I can say from my side is, like,
we see a lot of need for liquid
biopsy, for non-invasive
methods, and we see that they,
are correlating with cancers.
Yeah. Mhm, I'd say mine is
the promise of successes, of pre competitive
collaboration, bringing together groups to
have power for large studies. I
think every time we see a success in this
regard, it lays the groundwork for future
potential successes. And I think that if we
can get the lawyers to all agree
on terms, then,
I think that's the hard part is to make sure
that the interest of each of the
partners is respected and we're able to get
benefits from it. But I'm very
optimistic about that. It is
optimistic time. Well, thank you for
joining us. Thank you very much.
Thank you for listening
to the Proteomics in Proximity podcast
brought to you by OLink Proteomics. To
contact the host or for further information,
simply email
info@olink.com.