The Multi-omics
revolution
By Deborah
Grainger Ph.D
c
urrently, genomics studies contribute the vast majority of precision medicinebased data. As of August 2016, over 2,500 genome wide association studies (GWAS)
have published their findings in the literature 1. And this figure is set to rise as
improvements in next generation sequencing (NGS) technologies continue to reduce the
cost and turnaround time per genome sequenced. Add to this the parallel leaps and bounds
being made in bioinformatics and computational capacity and one essentially has the
blueprints for a genomic golden era, which can only mean good things for precision
medicine. However, although genomics big data offers a pretty comprehensive snapshot
of what precision medicine entails at present, the discipline is set to encompasses much,
much more than DNA-based data.
Underneath the buzz and excitement generated by genomics data, and the valuable ground being gained with them, there are other engines at
work in the field. These represent a largely unheralded revolution taking place; one which, despite the lack of fanfare, is poised to change the
shape of precision medicine for good. But rather than a revolution borne of one discipline in particular, it is in fact the combination of several:
it is proteomic, lipidomic and it is metabolomic too. It’s a charge that rallies multiple omics, or multi-omics, to its cause; it is a call for unison…
and diversification.
Biomarker discovery
Those heeding this call are scientists like Tony Whetton, one of the masterminds behind the recently opened Stoller Biomarker Discovery
Center at the University of Manchester. The Center is set to “develop an ecosystem” for biomarker discovery in the context of precision medicine.
Moreover, it is poised to do this using a multi-omics approach; “In terms of the search for biomarkers, we’re not only talking about a search for
genomic markers, but protein, metabolites and, potentially, lipid-based biomarkers too.” Whetton, a professor of cancer cell biology, who has
worked in the field of leukemia research for over 30 years, is clear on the direction The Stoller will take, “A multi-omics approach to precision
medicine is vital.”
Working alongside The Stoller’s scientists is the biotechnology company SCIEX, a world leader in mass spectrometry (a term often shortened to
‘mass spec’). SCIEX has provided The Stoller with thirteen high throughput (HTP) mass spectrometry platforms, which are being used to process
hundreds of patient protein samples per run. Aaron Hudson, Senior and General Manager of SCIEX Diagnostics, who has also been involved in
The Stoller project since its early conception, was also involved in the decision to take a multi-omics approach; he commented, “Much of the
precision medicine that is being done [at The Stoller], and at other centers around the world, is now looking beyond genomics. It’s not enough
just to look at DNA and RNA anymore; you’ve got to look at the way the whole body is interacting. You have to expand into proteins, lipids and
metabolites.”
Up until recently, it has been very difficult to
Unexpected Results
Director of Commercial Development at
perform the level of HTP screening required
For BERG the progression to multi-omics
Celera Genomics, a key industry partner in
by precision medicine-based approaches
was a simple philosophical matter as Narain
the Human Genome Project (HGP). “NGS
with mass spec instruments, but SCIEX has
explained, “Before we make decisions as
is a ‘hot’ area and it’s what you always hear
done a lot to improve capacity and data
doctors and scientists, we need to learn as
about, but you never hear about proteomics
processing in this area. One of the devel-
much as we can about the entire biological
in a broad way; you never hear about tumor
opments that has drastically increased the
narrative.” He then went onto describe how
biology either, because people are reluctant
amount of data obtained per mass spec run
the Interrogative Biology® platform uses
to work with live, fresh tissues.” Helomics™’
is the company’s proprietary SWATH analysis
artificial intelligence (AI) to drive hypoth-
unique contribution to the multi-omics
technology. Said Hudson of the platform,
esis -free therapeutic discovery. To do this
sphere involves working with such tissues.
“SWATH enables the quantification of up to
BERG collects hundreds, if not thousands,
Its Precision Cellular Analytical Platform
5,000 proteins across hundreds of samples,
of healthy and diseased samples and, in
(PCAP™) maintains tumor samples outside
and does it reproducibly.” Without this
addition to genomic information, obtains
of the body, as ‘virtual patients’. Rather than
reproducibility, analyzing mass spec data is
proteome, lipidome and metabolome
providing a snapshot of a tumor as fixed
akin to “looking for a needle in a haystack,”
data from them as well as information on
samples do, the platform is able to capture
he added. SCIEX has also developed a similar
mitochondrial function, oxidative states,
a ‘feature-length’ movie of tumors as they
solution for lipidomics as well: “We’ve now
and ATP production (a read-out of cellular
grow and change in real-time. This approach
launched a platform that can quantify 1,300
energy levels). This unstructured, big data
maintains the individuality of each tumor
lipid species in about 20 minutes in hundreds
is then processed by the AI built into the
sample and allows Helomics™ to perform
of samples.” Hudson confirmed. SCIEX is
Interrogative Biology® platform, “What
full, comprehensive tumor profiling and
so committed to bringing multi-omics data
we’re doing is asking the biology, not just
reliably interrogate tumor vulnerability with
processing up to speed that it has recently
the genes, what has gone wrong in the dis-
different classes of drugs, sparing the patient
partnered with NGS experts Illumina to bring ease state, and what can be done to fix it.”
unnecessary, grueling trials of different drug
SWATH computing to more users via a cloud
regimens.
solution called OneOmics.
Whilst these advances in sample processing
Narain cautioned that this approach may
throw out a few surprises; take one of the
PCAP™’s live cell tumor profiling capabilities
diabetes drugs in BERG’s research and
also highlight why a multi-omics strategy is
and data handling have moved things forward development pipeline for example. When
superior to one solely based on genomics.
considerably in terms of protein and lipid
AI algorithms identified an enzyme called
“There are driver mutations and passenger
analysis, Hudson admits these still have some
enolase as a potential drug target for dia-
mutations that are, respectively, either more
way to go before they are at the same stage
betes, a lot of head scratching was done.
active or passive in a disease state. You might
as genomic sequencing. Niven Narain, CEO
Here was data pointing to an intermediary
be a breast cancer patient whom genomic se-
and Co-Founder of BERG Health, a company
enzyme sitting in the middle of a metabol-
quencing has identified as a BRCA1 or 2 gene
that develops precision therapeutics using its
ic pathway. “We had our doubts, but we
mutation carrier, but the real question is: is
own multi-omics-based solutions, holds a
couldn’t build this amazing platform and be
your mutation transcribing and causing
similar view on the current progress being
biased, so we carried on and now the drug is
change to proteins downstream?” Campbell
made with multi-omics approaches. In 2008
validated at the preclinical stage.” The drug’s
explained further, “If the answer to that
Future Directions
As new multi-omics programs such as The
As molecular profiling ‘technologies’ both
done on a one-off basis. Laying all that into
Stoller Biomarker Discovery Center’s begin
proteomic and ‘genomic’ are becoming
a real workflow for every cancer patient no
to reveal new biomarker data, and as com-
more ‘commoditized’ more patients are
matter where they live, is what needs to be
panies like BERG Health and Helomics™
now getting access to them than if they
done.”
continue to see ‘theranostic’ success with
were solely available at the top-flight cancer
their multi-omics platforms, we may begin
centers; however, there’s still no infrastruc-
to see more multi-omics strategies become
ture out in the community for patients to
available as more innovation takes place in
access them routinely.”
the field.
This is the space Perthera, a company Petricoin cofounded, aims to occupy, revolutionizing patient access to multi-omics technologies by orchestrating the entire precision
In Petricoin’s view what’s needed isn’t more
medicine process for them. Perthera doesn’t
Yet for Emmanuel Petricoin, the Co-Di-
new multi-omics technologies per se, but a
practice medicine or treat the patient, but
acts on their and their physician’s behalf,
BERG launched its Interrogative Biology®
mechanism of action has since been shown
question is yes, you have a driver mutation
rector of the Center for Applied Proteom-
third-party to oversee them. A precision
platform, which brought one of the first
to increase glucose transporting proteins
and need to be treated accordingly. But if it’s
ics and Molecular Medicine (CAPMM) at
medicine ‘orchestra conductor’ or ‘traffic
with their express permission, to acquire
multi-omics solutions to the market, but
GLUT2 and GLUT4 in skeletal muscle and
no, and it’s a passenger mutation, literally
George Mason University, it is not a lack of
control cop’ that coordinates the whole
the patient’s tissue from the pathology lab
Narain is concerned that not enough have
hence increase glucose disposal to this tissue
just sitting along for the ride, your physician
upcoming technology and industry involve-
process from start to finish. He rationalised,
or schedule a biopsy with interventional
radiology. Perthera then sends samples of
followed in BERG’s footsteps, “I would argue
from the bloodstream. “So the multi-om-
needs to take this into consideration when
ment hindering the uptake of multi-omics
“Coordinating with pathologists and inter-
that after eight years, multi-omics needs are
ics approach really works, it can be done,”
identifying the best treatment for you.”
solutions; rather, it is due to a lack of ac-
ventional radiologists and surgeons, arrang-
this tissue to a host of different CLIA/CAP
still not being met. If you mention ‘lipid-
Narain concluded.
Multi-omics approaches can differentiate
cess. Said Petricoin: “The vast majority of all
ing biopsies, figuring out which multi-omics
accredited labs it has handpicked to perform
between patients in this way as they take
cancers in the US are treated at the
companies to send tissue to, then collating
genomic, proteomic and phosphoproteomic
proteins into consideration too, an area where
community level; these patients are not
and aggregating all the results and then
genomic and proteomic analyses, and will
Helomics™’ PCAP™ technology excels as
going to the MD Andersons or the Memorial
relating that data to the most up-to-date
soon be “layering on an RNASeq transcrip-
it monitors protein-protein interactions
Sloan Ketterings of the world to be seen,
science, is difficult even for one patient and
tomic analysis.”
anywhere in the cell, as they’re happening.
they’re being treated out in the community.
it’s likely to only be
omics’ or ‘metabolomics’ to people, sure,
they’ve heard those terms and there may be
several related projects out there, but how
many big pharma companies are involved?”
Living Multi-omics
Also advocating the multi-omics route is
Helomics™ President and CEO Neil Campbell,
whose résumé also includes time as Senior
Image supplied courtesy of SCIEX. © 2016 AB SCIEX.
All the data produced by this process is sent
is not to say it must shift entirely. Campbell
back to Perthera, which also receives the
is in agreement, “Although genes are not the
patient’s previous treatment history detailing
full equation, they are definitely part of the
former therapeutic regimens and any toxic-
equation.” Petricoin echoed this, “DNA is the
ities experienced. These data are aggregated
information archive, but it’s the proteins that
into a report which is sent to a cloud-based,
do the work and indeed are the drug targets
virtual tumor board, made up of medical
for nearly every targeted inhibitor and im-
experts from anywhere in the world. This
munotherapy. The first will give you an idea
panel of experts then provides a schema of
of what you’re looking at, the latter will give
ranked treatment options, which can include
you direct information about the state of a
anything from an FDA-approved drug the
disease and the molecular target that is the
patient hasn’t tried yet to an off-label one,
most ‘actionable.’”
all the way down to matched clinical trials
filtered for geographical proximity to the
patient. “We don’t tell the doctor what to
do,” explained Petricoin. “But we remove the
stress and hassle of coordinating multi-omics
precision medicine from the patient and
their doctor…”
Narain also believes that precision medicine is on the right track, but it will still
throw out a few surprises as it heads further
towards multi-omics: “It’s slowly moving
in the right direction; however, we need to
go way deeper than just genomics and get
used to the idea of a few unexpected finds.
Because Perthera is not a commercial lab, or
If we could make those small but funda-
indeed, a lab at all, it sits at the top of this
mental changes in the way that we approach
process and can pick and choose from the
precision medicine, then we’ll be making
companies and institutions that it feels are
progress.”
the most synergistic – “Those that provide
the most multi-omics solutions,” Petricoin
elaborated. As long as the technologies are
commercially available and CLIA/CAP accredited, they can be considered. “We don’t
have any financial connections with any of
these companies, we keep an arms-length
relationship with them. This enables us to
stop using any of the technologies the
second they become obsolete.” He further
added, “Perthera is driven to identify
companies that are offering the best
(*A research field combining therapeutics
and diagnostics.)
References
1. Welter D, MacArthur J, Morales J, Burdett T, Hall P,
Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L,
and Parkinson H.The NHGRI GWAS Catalog, a curated
resource of SNP-trait associations. Nucleic Acids
Research, 2014, Vol. 42 (Database issue): D1001-D1006.
CLIA = the Clinical Laboratory Improvement Amendments of 1988 are United States federal regulatory
standards that oversee and grant accreditation for l
aboratory developed tests (LDTs). They apply to all
clinical laboratory testing performed on humans in the
United States, except clinical trials and basic research.
molecular profiling solutions; we would
CAP = College of American Pathologists
be out of business if we didn’t constantly
Theranostics = A research field combining diagnostics
and therapeutics, in which molecular diagnostic tests
are developed in tandem with targeted therapeutics.
survey the field to ensure our patients and
their treating oncologists are armed with
the absolute best multi-omic data to make
the best treatment decisions.”
Shifting The Balance
Deborah Grainger, Ph.D, is an independent science
writer with a wide-ranging subject interest. Equally
comfortable covering topics from complex neuroscience
to drug combinations in immune oncology, she honed
With the democratization of precision
her writing skills working in communications for five
medicine and its centralization into ‘hub’
years at a biotechnology SME. Deborah also holds a
companies like Perthera, the balance may
PhD in cell signaling from the University of Manchester.
shift further towards multi-omics, becoming
Reprinted with Permission from The Journal of Precision
less weighted in favor of genomics. But that
Medicine September/October 2016