ILLUMINA CASE STUDYKATHLEEN C. BARNES, PHD

DNA methylation changes
associated with COVID-19
Disease classifiers based on DNA methylation patterns offer
the potential to predict clinical outcomes.

Introduction
Kathleen Barnes, PhD wants to “disentangle the genetic underpinnings that contribute to health disparities.” It was this focus that led
her to the Colorado Center for Personalized Medicine (CCPM). One
goal of the CCPM is to link extensive electronic medical records
with multiomics information to accelerate discoveries that will
improve human health and fundamentally change the way medicine
is practiced. To this end, CCPM established a CLIA- and CAP-certified biobank in collaboration with UCHealth. When COVID-19 took
the world by surprise, this biobank placed Dr. Barnes and her colleagues in a unique position to continue their research efforts whilelooking for ways to battle the SARS-CoV-2 virus.
Kathleen C. Barnes, PhD is theFounding Director of the Colorado
Center for Personalized Medicine(CCPM) at the University of Colorado
Anschutz Medical Campus andSenior Vice President, Population
Health Genomics at Tempus Labs

Moving towards methylation in infectious disease
Prior to the pandemic, the CCPM team had partnered with Illumina
to explore options for introducing clinical methylation-based testingfor tumor classification and diagnostics into the CCPM Biobank.
The day of the shutdown, Dr. Barnes read an article about theepigenetics of COVID-19. She immediately shifted her research tomethylation and infectious disease.

A mad scramble for biospecimens
One of the biggest challenges to this study was obtaining samples.
“There was a mad scramble to access biospecimens from COVIDpatients,” states Dr. Barnes. With a biobank-fueled collaboration,
the team theorized, “because it’s infectious disease, we should beable to use blood,” which turned out to be easier than capturingleftover nasal pharyngeal samples. They also had a reliable healthdata warehouse through which they could track whether thesubjects that they received samples from were tested for COVID-19
and if they were positive or negative for the virus.

For Research Use Only. Not for use in diagnostic procedures.

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Overview

Using an Illumina solution

SARS-CoV-2 infection generatesa specific, detectable epigenetic
signature in the hostAs experienced Illumina users, who had even contributed content
to the Infinium™ Multi-Ethnic Global Array, Dr. Barnes' team began
the COVID studies by customizing the Infinium MethylationEPIC
BeadChip. “We added about 7800 CpGs representing genes that
we thought would be relevant, not just for SARS-CoV-2 infection,
but infectious disease in general, and we called this EPIC+.”

Challenge
PCR -based techniques for
COVID-19 testing do not detect
this signature
SolutionCustomize the Infinium
MethylationEPIC BeadChip todetect and classify differential host
DNA methylation patterns thatarise due to SARS-CoV-2 infection
Benefits
Understand the potential ofmeasuring methylation signatures
for detecting and predicting thecourse of viral infections

The importance of the methylome"Even though there’s been a lot work to study infectious disease,
we felt like the methylome hadn’t been fully exploited…and methylation quantification, using the EPIC+ BeadChip, is actually pretty
affordable at scale. The relationship between methylation patterns,in the presence or absence of a disease, is potentially as informative as other diagnostics platforms and we imagined that this could
be scaled to address the pandemic,” states Dr. Barnes.
One of the major findings is that DNA methylation profiling, inconjunction with machine learning techniques, can identify a SARSCoV-2 specific epigenetic signature. “We’ve been able to demonstrate high sensitivity and specificity in predicting an infection,
and also in-hospital clinical deterioration,” states Dr. Barnes. “Ourfindings suggest that measuring methylation signatures, during
and after SARS-CoV-2 infection, can provide clinicians with theability to detect viral infection, as well as predict that patient’s
clinical course."

Read the paper
Konigsberg IR, Barnes B, Campbell M, et al. Host methylation
predicts SARS-CoV-2 infection and clinical outcome. Preprint at
www.researchsquare.com/article/rs-334297/v1. Posted March 22,2021. Accessed September 8, 2021.

Learn more
Infinium MethylationEPIC BeadChip, www.illumina.com/products/by-type/microarray-kits/infinium-methylation-epic.html
Dr. Barnes, CCPM, creating a BeadChip, and COVID, www.illumina.
com/content/dam/illumina-marketing/documents/icommunity/methylation-covid-barnes-interview-m-gl-00158.pdf
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For specific trademark information, see www.illumina.com/company/legal.html.
M-GL-00167 v1.0

For Research Use Only. Not for use in diagnostic procedures.

M-GL-00167 v1.0| 2

1.800.809.4566 toll-free (US) | +1.858.202.4566 tel | techsupport@illumina.com | www.illumina.com© 2021 Illumina, Inc. All rights reserved. All trademarks are the property of Illumina, Inc. or their respective owners.
For specific trademark information, see www.illumina.com/company/legal.html.
M-GL-00167 v1.0

M-GL-00167 v1.0

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