Ebook ThePowerOfMultiomics

The power of
multiomics
More to see.
More to understand.
More with multiomics.
For Research Use Only. Not for use in diagnostic procedures. M-GL-00120 v1.0 | 1
THE POWER OF MULTIOMICS
Table of contents
3 Why adopt multiomics
4 Multiomics multiplies your discovery power
5 Multiomics is more accessible than ever
7 How multiomics is fueling discovery
7 Genomics + transcriptomics
8 Genomics + epigenetics
10 Epigenetics + transcriptomics
11 Transcriptomics + proteomics
13 Genomics + proteomics
14 See how more scientists are using multiomics
15 What’s next for multiomics
15 Increasing access to multiomic insights
18 Select multiomic methods
20 Summary
20 References
2 | M-GL-00120 v1.0 For Research Use Only. Not for use in diagnostic procedures.
Introduction “Single omics can be

useful for straightforward
questions, but for some of
Advances in genomic technologies are giving researchers the tools to the most complex problems
access more molecular data than ever before, enabling transcriptomics, in biology, you want to
epigenetics, proteomics, and beyond. To see the full picture of biology, have as much information
scientists are increasingly turning towards a multiomic approach that as possible. That’s where
integrates these various omic methods. This eBook provides examples multiomics really shines.”
from the scientific literature of how multiomics can provide unique
discovery power for deeper biological insights and comprehensive answers Danny Wells, PhD
to mechanisms of disease. Scientific Co-Founder and Senior
Vice President of Strategic Research,
Immunai
Why adopt multiomics
Biology is multilayered and complex. The central dogma reiterates the

intertwined relationship between DNA, RNA, and protein. Genetic variation
at the DNA level can impact RNA expression or protein function in diverse
and unpredictable ways. Environmental factors can also alter regulatory
pathways and cellular metabolism to affect biology and human health.
Multiomics provide a different perspective to power discovery across

multiple levels of biology. This biological analysis approach combines
genomic data with data from other modalities measuring gene expression,
gene activation, and protein levels to enable a more comprehensive
understanding of molecular changes contributing to normal development,
cellular response, and disease. Using multiomics, researchers can better
connect genotype to phenotype and fuel discovery of novel drug targets
and biomarkers.
Multiple layers of informa-

tion connect genotype to
phenotype—Combining DNA,
epigenetics, RNA, protein, or
other molecular measurements
into a full cellular readout
provides researchers with novel
scientific insights that cannot be
found from single omic methods
alone.
“I think the thing that is cool Multiomics multiplies your discovery power
about using multiomics is
that it gives you multiple Massively parallel genomic technologies, like next-generation sequenc-
views into the same ing (NGS) and microarrays, have expanded the scope and scale of what
problem. It’s like in reality— researchers can study to include whole genomes, exomes, transcriptomes,
the world happens in epigenomes, and more. Each modality is a piece of the puzzle offering
multiomics.” important insights into the details of biological and disease mechanisms.
Additionally, high-resolution approaches like single-cell sequencing or
Pejman Mohammadi, PhD spatial analysis offer another layer of fundamental detail to examine het-
Associate Professor of Computational erogeneity in complex cell populations.
Biology, Scripps Research
Through the combined lens of multiomics, researchers can witness the
v complicated interplay between the molecules of life. Integrating these
complementary metrics into multiomic data sets brings a more compre-
hensive picture of cellular phenotypes and helps pull more high-quality
information from each sample.
Bigger picture biology through multiomics—Multiomics goes beyond the genome to

unlock deeper biological insights. Using every piece of molecular data available can
accelerate biological discoveries and transform our understanding of human health.
Multiomics is more accessible than ever “My advice is to dive right in.
Multiomic workflows have
The cost of sequencing has decreased tremendously over the past become quite standard and
decade, enabling sequencing studies of greater scale and depth as well just about anybody can
as new applications. The scientific community can generate more detailed do this type of work. The
data from their samples or interrogate their samples at multiple levels for field is moving so quickly, if
greater insights. you wait for a time when it
seems like it’s mature, it will
Trends in multiomics grant funding and publications already have moved on to
the next great thing.”
In part due to the decreasing cost of sequencing technologies and the
speed at which they generate data, more labs are adopting multiomics. The Ben Humphreys, MD, PhD
rapid rise of multiomic approaches is evidenced by a growing presence in Chief of the Division of Nephrology,
the current literature and an expanding share of grant funding. Washington University in St. Louis
Multiomics publications on the rise—Since 2012, there has been a 63% average year-
over-year increase in the number of publications featurning multiomic data.
“The opportunities to
understand the biology
of different cell types by
combining multimodal data
sets are extremely exciting.
This allows us to uncover
a much deeper level of
biology.”
Ben Humphreys, MD, PhD

Chief of the Division of Nephrology,
Washington University in St. Louis
Grant funding growth for multiomics—Since 2012, there has been a 48%
average year-over-year increase in the number of active or starting grants for
multiomic studies.
How multiomics is fueling discovery “We most definitely have

found things we would
have missed had we not
Scientists using multiomics are able to make discoveries they may have used a multiomic approach.”
missed if using a single method alone. Here we highlight the most common
multiomic combinations and share examples from recent literature to Minoli Perera, PharmD, PhD
demonstrate how multiomics is providing novel insights into biological Associate Professor, Northwestern
function and disease mechanisms. University Feinberg School of
Medicine
Genomics + transcriptomics
Genome-wide association studies (GWAS) have successfully identified

genetic variants associated with complex diseases. The genotype offers
information on susceptibility to the disease; however, determining the
specific genes and pathways affected by those variants is more difficult.
Incorporating RNA sequencing (RNA-Seq) can help researchers annotate
and prioritize variants uncovered in GWAS for functional analysis to
understand mechanisms of disease. Gene expression analysis informs if
and when the genes of interest are down- or upregulated in the disease
samples. This multiomic approach to functional genomics can help power
drug target identification and biomarker discovery.
Basic science researchers combining genomics + transcriptomics—Of researchers

focused on genomics methods (blue), 74% also use transcriptomics methods. Of
researchers focused on transcriptomics methods (dark pink), 46% also use genomics
methods.1
“We hope that our single- MULTIOMICS RESEARCH EXAMPLE

cell multiomic studies will
ultimately impact patients
by identifying therapeutic
pathways that are targetable
by drugs. This will lead to
discovery programs and Methods: WES + single-cell RNA-Seq
clinical trials to create drugs
that will improve the lives of Dissecting the origins of immune cells involved in organ transplant
patients around the world.” rejection
Ben Humphreys, MD, PhD Researchers at Washington University School of Medicine combined bulk
Chief of the Division of Nephrology, whole-exome sequencing (WES) and single-cell RNA-Seq to tease apart
Washington University in St. Louis details of the immune cell response during kidney transplant rejection.2
In solid organ transplant, it’s not known whether donor-derived immune

cells decline with time after surgery or persist and play a role in rejection.
Previous techniques to distinguish immune cells originating from donor or
recipient were limited to sex-mismatched transplants and relied on identi-
fying the Y chromosome. With a multiomic approach, WES determined
genetic variation between donor and recipient. Then, by sequencing
transcripts from individual immune cells from human kidney biopsies,
researchers could match the single nucleotide variants in expressed genes
to identify cell origin.2
Single-cell immune profiling was used to look at the transcriptomes of

over 80,000 cells simultaneously, including over 5000 macrophages and
3600 lymphocytes. Recipient-origin macrophages and T-cells showed
distinct proinflammatory gene expression patterns and donor-derived cells
could persist for years after organ transplant. Understanding the mecha-
nisms of organ transplant rejection could lead to more targeted immuno-
suppression drugs.2
Genomics + epigenetics
The majority of human variation identified by GWAS is in the noncoding

regions of the genome, including introns, promoters, or enhancers. Com-
prehensive epigenetic profiling can reveal patterns of gene regulation to
help find the function of those variants. NGS-based epigenetic techniques
include chromatin immunoprecipitation (ChIP-Seq), assay for transposase-
accessible chromatin (ATAC-Seq), and chromosome conformation
capture (Capture C, HiC). DNA methylation patterns are also conserved
and can represent a new class of biomarkers. Multiomic approaches that
combine methylation, or other epigenetic profiling, with genetic informa-
tion can connect functional layers to decipher complex pathways and
disease mechanisms.
“A multiomic approach
increases our understanding
of biology by helping us
see things that would be
hidden with one type of
data.”
Pejman Mohammadi, PhD

Associate Professor of Computational
Basic science researchers combining genomics + epigenetics—Of researchers

focused on genomics methods (blue), 38% also use epigenetics methods. Of
researchers focused on epigenetics methods (light pink), 53% also use genomics
methods.1
MULTIOMICS RESEARCH EXAMPLE
GWAS + methylation arrays
Methylation risk score improves prediction of major depressive disorder
A study led by a team at the University of Edinburgh built upon GWAS and
explored how epigenetic markers contribute to risk for major depressive
disorder.3
Variation in DNA methylation is associated with lifestyle risk factors for

depression, such as smoking and body mass index (BMI), thus methylation
patterns can capture a “record” of these environmental influences. Using
the Infinium™ MethylationEPIC Array from Illumina, researchers determined
the genome-wide CpG methylation signatures of 9873 samples from
Generation Scotland: the Scottish Family Health Study.3
Based on longitudinal phenotypic data, the calculated “methylation risk

score” additively improved prediction of depression when combined with
risk scores based on genetic variation. Methylation explained 1.75% of the
variance seen in major depression and remained significant even after
adjusting for lifestyle factors. This study demonstrates that using a risk
score based on multiomic data sets can offer greater clinical power to
predict and potentially prevent major depressive disorder.3
Epigenetics + transcriptomics
Epigenetics and transcriptomics offer complementary information to study

Unify single-cell gene expression the details of cellular differentiation and response. Combining epigenetic
and chromatin accessibility and RNA-Seq methods allows researchers to directly measure the ties
Enable RNA-Seq and ATAC-Seq between gene regulation and gene expression, instead of simply inferring
measurements from the same single those connections. Integrating epigenetics and RNA-Seq can help re-
cells in the same assay. searchers identify candidate genes and understand the mechanisms
controlling interesting phenotypes. This holistic, non-biased multiomics
Read Technical Note approach can uncover new regulatory elements for biomarkers and thera-
peutic targets.
Basic science researchers combining epigenetics + transcriptomics—Of researchers

focused on epigenetics methods (light pink), 77% also use transcriptomics methods.
Of researchers focused on transcriptomics methods (dark pink), 34% also use epi-
genetics methods.1
ChIP-Seq + Total RNA-Seq
Epigenetic landscape associated with Alzheimer’s disease
A research team from the University of Pennsylvania led a multiomics study

to examine epigenetic dysregulation in early Alzheimer’s disease. Even
though protein aggregation is a hallmark of Alzheimer’s disease, therapies
that target those proteins have not been effective.4
Comparing healthy older and younger postmortem brain tissue with

tissue from brains of Alzheimer’s patients, this team performed total
RNA-Seq and epigenetic sequencing assays, including ChIP-Seq and
5-hydroxymethylcytosine (5hmC) analysis.4
Results showed that a reconfiguration of the epigenomic landscape occurs

with Alzheimer’s disease. Certain transcription- and chromatin-
related genes are upregulated, which then disable protective pathways
of healthy aging and initiate epigenetic changes that drive disease. The
discovery of these regulatory feedback loops suggests potential epigene-
tic strategies for early intervention against Alzheimer’s disease.4
Transcriptomics + proteomics
RNA-Seq offers unparalleled discovery power to interrogate the tran-

scriptome without prior knowledge. Incorporating protein detection with
RNA-Seq can tie new discoveries back to known canonical markers and Simultaneous bulk protein and gene
historical clinical outcomes. expression profiling
BEN-Seq method uses Illumina NGS
Antibodies tagged with oligonucleotide barcodes enable analysis of cell and oligo-conjugated antibodies for
surface proteins with results read by sequencing, which scales to a much easy quantification of multiple protein
higher number of parameters than flow cytometry or mass cytometry. targets.
Methods like CITE-Seq (cellular indexing of transcriptomes and epitopes
by sequencing) combine single-cell RNA-Seq with cell surface protein Read Application Note
analysis. BEN-Seq (bulk epitope and nucleic acid sequencing) is performed
at the bulk level. Spatial transcriptomics interrogates RNA and proteins in
context with tissue morphology.
Protein detection with sequencing—DNA-tagged antibodies allow for detection of

cell surface proteins with results read by sequencing. When cell surface markers
are more robustly analyzed through multiomics, there are two chances to catch an
important signal.
“We chose a multiomic

approach because the
complexity of the immune
system demands it. There
are some populations of
immune cells that can only
be read out in a particular
type of omic technology.”
Danny Wells, PhD

Scientific Co-Founder and Senior
Vice President of Strategic Research,
Immunai
Basic science researchers combining transcriptomics + proteomics—Of researchers

focused on transcriptomics methods (dark pink), 66% also use proteomics methods.
Of researchers focused on proteomics methods (violet), 64% also use transcriptomics
methods.1
Spatial RNA-Seq + spatial protein analysis
Uncovering spatial heterogeneity in SARS-CoV-2 lung infection
A research group at Massachusetts General Hospital used spatial multio-

mics to examine the relationship between SARS-CoV-2 lung infection and
the severity of pulmonary disease.5
The team performed spatial molecular analysis of both RNA and protein
in 24 lung specimens from autopsies of COVID-19 patients. Using a
spatial profiling system, they looked at over 1800 RNA markers to identify
cell regions with high or low viral load. The researchers also examined
79 protein markers to identify immune cell phenotypes in different lung
regions.5
The combined data uncovered spatial relationships between virus location

and immune cell abundance, suggesting two phases of infection. During
early infection, high levels of virus triggered expression of interferon-
related genes. A later phase showed surprisingly little viral replication in the
lungs, but severe tissue damage. These details may help scientists learn
how COVID-19 can be fatal.5
Genomics + proteomics “In the future, I’m looking

forward to modeling large-
This multiomic approach directly connects genotype to phenotype for scale data sets that come
more informed research on disease and therapeutics development. Linking from the transcriptome,
genetic variation to protein expression at the single-cell level can reveal the proteome, and even
the functional impact of somatic mutations on human cancers to better the metabolome. This
understand tumor evolution and disease progression. will help us understand
how different types
of biomolecules are
connected to each other in
a mechanistic way.”
Pejman Mohammadi, PhD

Associate Professor of Computational
Basic science researchers combining genomics + proteomics—Of researchers

focused on genomics methods (blue), 63% also use proteomics methods. Of re-
searchers focused on proteomics methods (violet), 38% also use genomics methods.1
Single-cell targeted resequencing + single-cell cell surface protein analysis
Tracking clonal evolution in myeloid cancers
Scientists at Memorial Sloan Kettering Cancer Center and the University

of California San Francisco applied single-cell multiomics to track clonal
evolution in 146 samples from 123 patients with myeloid cancers. Oligo-
conjugated antibodies enable high-throughput single-cell proteomics with
sequencing. Using targeted sequencing panels, this group performed
simultaneous single-cell mutational analysis and cell-surface protein
quantification for more than 740,000 cells. This level of scale and detail
coupling genotype with phenotype allowed the researchers to finely map
the dynamics of cancer cell clonal complexity and its effect on disease
progression.6
See how more scientists are using multiomics
Multiomics is revolutionizing research and pushing limits with novel scientific insights that make new discoveries possible.
Explore additional examples from the literature demonstrating the power of multiomic approaches that combine two, three,
or more modalities.
Genomics + transcriptomics
Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma
Jerby-Arnon L, Neftel C, Shore M, et al. Nat Med. 2021;27(2):289-300. doi:10.1038/s41591-020-01212-6
Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease
Bryois J, Skene NG, Hansen TF, et al. Nat Genet. 2020;52(5):482-493. doi:10.1038/s41588-020-0610-9
Genetic identification of brain cell types underlying schizophrenia
Skene NG, Bryois J, Bakken TE, et al. Nat Genet. 2018;50(6):825-833. doi:10.1038/s41588-018-0129-5
Genomics + epigenetics + transcriptomics

Epigenome-wide association study identifies cardiac gene patterning and a novel class of biomarkers for heart failure
Meder B, Haas J, Sedaghat-Hamedani F, et al. Circulation. 2017;136(16):1528-1544. doi:10.1161/CIRCULATIONAHA.117.027355
Epigenetics + transcriptomics
Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney
Muto Y, Wilson PC, Ledru N, et al. Nat Commun. 2021;12(1):2190. doi:10.1038/s41467-021-22368-w
Single-cell multiomics sequencing reveals the functional regulatory landscape of early embryos
Wang Y, Yuan P, Yan Z, et al. Nat Commun. 2021;12(1):1247. doi:10.1038/s41467-021-21409-8
Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
Rydbirk R, Folke J, Busato F, et al. Acta Neuropathol Commun. 2020;8: 29. doi: 10.1186/s40478-020-00908-7
Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density
Chesi A, Wagley Y, Johnson ME, et al. Nat Commun. 2019;10(1):1260. doi:10.1038/s41467-019-09302-x
Epigenetics + transcriptomics + proteomics

Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq
Swanson E, Lord C, Reading J, et al. Elife. 2021;10:e63632. doi:10.7554/eLife.63632
Transcriptomics + proteomics
Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19
Su Y, Chen D, Yuan D, et al. Cell. 2020;183(6):1479-1495.e20. doi:10.1016/j.cell.2020.10.037
Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis
Trzupek D, Dunstan M, Cutler AJ, et al. Genome Med. 2020;12(1):55. doi:10.1186/s13073-020-00756-z
Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells
Mimitou EP, Cheng A, Montalbano A, et al. Nat Methods. 2019;16(5):409-412. doi:10.1038/s41592-019-0392-0
Genomics + proteomics
Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia
Demaree B, Delley C, Vasudevan H, et al. Nat Commun. 2021;12(1):1583. doi:10.1038/s41467-021-21810
Integrating human brain proteomes with genome-wide association data implicates new proteins in Alzheimer's disease pathogenesis
Wingo AP, Liu Y, Gerasimov ES, et al. Nat Genet. 2021;53(2):143-146. doi:10.1038/s41588-020-00773-z
What’s next for multiomics
The multiomic methods and research examples highlighted here represent

a new holistic approach to understanding biology. As the cost of
sequencing continues to decrease and the technology advances,
multiomic assays will become more comprehensive and better integrated.
Labs will be able to study more samples under different conditions to
reveal dynamic properties of cells and systems. Sequencing will support
proteomic studies with oligo-tagged antibodies for hundreds to thousands
of markers. Single-cell multiomics will expand to a scale of millions of cells
per experiment. More assays will incorporate multimodal measurements at
higher resolution.
One of the biggest challenges for multiomic research is how to integrate

different molecular data sets in a standardized way. Researchers need
robust computational strategies to extract biologically meaningful insights
from these vast amounts of data. Sophisticated bioinformatics tools like
Seurat7 enable normalization and integration of multimodal single-cell
sequencing experiments. Machine learning methods will also help organize
and filter complex multiomic data.
The comprehensive view provided by multiomics will illuminate new bio-

markers and drug targets to advance precision medicine.
Increasing access to multiomic insights
How Illumina is powering multiomics
Illumina strives to accelerate impactful discoveries by delivering products

that increase access to genomic data insights across the globe. Our
scalable sequencing solutions enable data-rich methods like single-cell
analysis and multiomic approaches. Illumina is continuing to invest in major
technology innovations to provide integrative genomic capabilities and
remove typical workflow and informatics bottlenecks.
Illumina powers multiomic analysis with a solution suite that offers

industry-leading standards of data quality, flexibility, and scalability. The
common readout across NGS approaches permits integration of multiple
data types to help researchers maximize the genomic data potential for
valuable research samples.
Library prep and sequencing
Breakthrough innovations in library preparation for genome, exome, and

transcriptome sequencing help researchers extract greater insights from
Learn more about single-cell techniques multiomic approaches in less time. Illumina library prep workflows are easy
using Illumina sequencing platforms to use, scalable for any size lab, and require few steps.
Download the single-cell The NextSeq™ 2000, NextSeq 1000, and NovaSeq™ 6000 systems offer
sequencing eBook application flexibility to power multiomic approaches and make them more
affordable. These systems allow for exceptional breadth of targets and
scalability for sequencing at an accessible price point.
Bioinformatics
Explore Illumina bioinformatics solutions at The Illumina software and informatics portfolio includes some of the
illumina.com/products/by-type/ fastest, most accurate, and advanced solutions for analysis, interpretation,
informatics-products.html. and data aggregation.
The Illumina DRAGEN™ (Dynamic Read Analysis for GENomics) Bio-IT

Platform provides accurate, ultra-rapid secondary genomic analysis of
sequencing data.
BaseSpace™ Correlation Engine mines over 23,000 scientific studies to

get data-driven answers for genes, experiments, drugs, and phenotypes.
Researchers can analyze gene function across different species, and view
pathways that play a role in disease development across multiple studies
and data types.
Illumina Connected Analytics is a comprehensive cloud-based data

management and analysis software platform empowering researchers
to manage, analyze, and interpret large volumes of multiomics data in a
secure, scalable, and flexible environment.
Arrays
Illumina microarrays offer high-quality data and exceptional genomic

coverage to propel genomic studies of any size. Powered by widely
adopted Infinium technology, Illumina microarrays provide the trusted data
quality needed to accelerate research.
The Infinium MethylationEPIC Array quantitatively interrogates over

850,000 methylation sites for epigenome information to add to your multio-
mics study. Multiple samples, including formalin-fixed, paraffin-embedded
(FFPE) tissue, can be analyzed in parallel to deliver high-throughput power
while minimizing the cost per sample.
Arrays like the Infinium Global Diversity Array enable variant identification
and can be combined with another omic technology like transcriptomics or
epigenetics to help provide biological context to those variants.
Partnering to advance science further
Illumina offers integrated services and support to match the quality of our
proven technology. When you choose Illumina products, it’s the beginning
of a relationship. Our technical support lines are staffed with experts, Learn how Illumina can help you further
many with PhDs, and we have an extensive library of free online training your research at illumina.com/science/
resources. technology/next-generation-sequencing/
choose-ngs-company.html
Illumina is committed to supporting the breadth of applications across
the DNA and RNA continuum. Illumina technology also makes possible
emerging applications and multiomic approaches to sequencing, including
proteomics and methylation analysis. Through partnerships with vendors
such as BioLegend, 10x Genomics, Becton Dickinson, and Nanostring, we
help provide multiomics product solutions to fit your research needs.
Select multiomic methods
The following methods are building blocks for a multiomic experiment. Mix and match whole-exome sequencing with gene
expression profiling or ATAC-Seq. Perform omic analysis with single-cell or spatial resolution. Or choose a multimodal
approach like BEN-Seq or CITE-Seq with multiomic readouts built directly into the assay.
Method What you can do Learn More
Bulk genomics Whole-genome Obtain a high-resolution, base-by-base illumina.com/techniques/sequencing/dna-

sequencing view of the entire genome to capture both sequencing/whole-genome-sequencing.
large and small variants that might be html
missed with targeted approaches
Whole-exome Focus sequencing on the protein-coding illumina.com/techniques/sequencing/dna-

sequencing regions of the genome, which include sequencing/targeted-resequencing/exome-
~85% of known disease-related variants sequencing.html
Genotyping arrays Survey millions of markers in cohorts illumina.com/techniques/popular-

or populations to identify disease applications/genotyping.html
associations across the whole genome
Bulk epigenetics Methylation arrays Identify methylation sites across the illumina.com/techniques/microarrays/
genome at single-nucleotide resolution methylation-arrays.html
with extensive coverage of CpG islands,
genes, and enhancers for epigenome-
wide association studies
ChIP-Seq Identify DNA binding sites for illumina.com/techniques/sequencing/dna-

transcription factors and other proteins sequencing/chip-seq.html
ATAC-Seq Profile accessible chromatin using a illumina.com/techniques/popular-

hyperactive Tn5 transposase that inserts applications/epigenetics/atac-seq-
sequencing adapters into open regions of chromatin-accessibility.html
the genome
Single-cell Single-cell ATAC- Measure both gene expression and illumina.com/content/dam/illumina/gcs/

epigenetics + Seq + mRNA-seq chromatin accessibility at the single- assembled-assets/marketing-literature/10x-
transcriptomics cell level to reveal gene regulatory multiomics-tech-note-m-amr-00006/10x-
networks and provide insights into cell multiomics-tech-note-m-amr-00006.pdf
heterogeneity
Bulk transcriptomics Whole- Capture both coding and noncoding RNA illumina.com/techniques/sequencing/rna-
transcriptome transcripts to help idenitfy biomarkers and sequencing/total-rna-seq.html
sequencing better understand phenotypes of interest
(Total RNA-Seq)
mRNA-Seq Reveal alternative transcripts, gene illumina.com/techniques/sequencing/rna-

fusions, and allele-specific expression sequencing/mrna-seq.html
patterns with a clear, comprehensive view
of the coding transcriptome illumina.com/techniques/sequencing/
rna-sequencing/rna-exome-capture-
sequencing.html
Method What you can do Learn More
Bulk combined BEN-Seq Simultaneously profile cell surface illumina.com/content/dam/illumina/gcs/

transcriptomics proteins and gene expression to assembled-assets/marketing-literature/
+ proteomics understand the relationship between cell biolegend-ben-seq-app-note-m-gl-00024/
markers and RNA biolegend-ben-seq-app-note-m-gl-00024.
pdf
Single-cell CITE-Seq Use mRNA-Seq and oligo-tagged pages.10xgenomics.com/rs/446-PBO-704/

transcriptomics + antibodies to evaluate both gene images/10x_LIT089_Product-Sheet_
proteomics expression and protein levels Multiomic-Profiling_Letter_digital.pdf
simultaneously on a single-cell level
Spatial Spatial RNA-Seq Use spatial profiling to access RNA and nanostring.com/products/geomx-digital-
transcriptomics and protein analysis protein expression in different tissue spatial-profiler/applications/
+ proteomics sections for pathway analysis and
biomarker discovery
Single-cell Proteogenomics Link genomic variation to protein biolegend.com/Files/Images/BioLegend/

genomics + expression to reveal cell identities and totalseq/MissionBio_BioLegend_
proteomics inform disease research and therapeutics TotalSeq-D_App_Note.pdf
development
Summary
Multiomics is a rapidly emerging, transformative approach to life science

research powered by cutting-edge sequencing and array technology. In-
tegrating multiple omics research methods and data sets into your experi-
ments brings a more holistic view to understanding biology. Multiomic tools
enable limitless applications that are helping researchers discover novel
scientific insights.
References
1. Percepta Associates, Inc. Cell Biology Market Research. 2020.

2. Malone AF, Wu H, Fronick C, Fulton R, Gaut JP, Humphreys BD. Harnessing
expressed single nucleotide variation and single cell RNA sequencing to define
immune cell chimerism in the rejecting kidney transplant. J Am Soc Nephrol.
2020;31(9):1977-1986. doi:10.1681/ASN.2020030326
3. Barbu MC, Shen X, Walker RM, et al. Epigenetic prediction of major depressive
disorder. Mol Psychiatry. 2020;10.1038/s41380-020-0808-3. doi:10.1038/s41380-
020-0808-3
4. Nativio R, Lan Y, Donahue G, et al. An integrated multi-omics approach
identifies epigenetic alterations associated with Alzheimer's disease. Nat Genet.
2020;52(10):1024-1035. doi:10.1038/s41588-020-0696-0
5. Desai N, Neyaz A, Szabolcs A, et al. Temporal and spatial heterogeneity of host
response to SARS-CoV-2 pulmonary infection. Nat Commun. 2020;11(1):6319.
doi:10.1038/s41467-020-20139-7
6. Miles LA, Bowman RL, Merlinsky TR, et al. Single-cell mutation analysis of clonal
evolution in myeloid malignancies. Nature. 2020;587(7834):477-482. doi:10.1038/
s41586-020-2864-x
7. Stuart T, Butler A, Hoffman P, et al. Comprehensive integration of single-cell data.
Cell. 2019;177(7):1888-1902.e21. doi:10.1016/j.cell.2019.05.031
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.
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The power of

3 Why adopt multiomics

4 Multiomics multiplies your discovery power

5 Multiomics is more accessible than ever

7 How multiomics is fueling discovery

14 See how more scientists are using multiomics

15 What’s next for multiomics

15 Increasing access to multiomic insights

18 Select multiomic methods

Introduction “Single omics can be

Why adopt multiomics

Biology is multilayered and complex. The central dogma reiterates the

Multiomics provide a different perspective to power discovery across

Multiple layers of informa-

Bigger picture biology through multiomics—Multiomics goes beyond the genome to

Ben Humphreys, MD, PhD

How multiomics is fueling discovery “We most definitely have

Genome-wide association studies (GWAS) have successfully identified

Basic science researchers combining genomics + transcriptomics—Of researchers

“We hope that our single- MULTIOMICS RESEARCH EXAMPLE

In solid organ transplant, it’s not known whether donor-derived immune

Single-cell immune profiling was used to look at the transcriptomes of

The majority of human variation identified by GWAS is in the noncoding

Pejman Mohammadi, PhD

Basic science researchers combining genomics + epigenetics—Of researchers

MULTIOMICS RESEARCH EXAMPLE

GWAS + methylation arrays

Methylation risk score improves prediction of major depressive disorder

Variation in DNA methylation is associated with lifestyle risk factors for

Based on longitudinal phenotypic data, the calculated “methylation risk

Epigenetics and transcriptomics offer complementary information to study

Basic science researchers combining epigenetics + transcriptomics—Of researchers

MULTIOMICS RESEARCH EXAMPLE

ChIP-Seq + Total RNA-Seq

Epigenetic landscape associated with Alzheimer’s disease

A research team from the University of Pennsylvania led a multiomics study

Comparing healthy older and younger postmortem brain tissue with

Results showed that a reconfiguration of the epigenomic landscape occurs

RNA-Seq offers unparalleled discovery power to interrogate the tran-

Protein detection with sequencing—DNA-tagged antibodies allow for detection of

“We chose a multiomic

Danny Wells, PhD

Basic science researchers combining transcriptomics + proteomics—Of researchers

MULTIOMICS RESEARCH EXAMPLE

Spatial RNA-Seq + spatial protein analysis

Uncovering spatial heterogeneity in SARS-CoV-2 lung infection

A research group at Massachusetts General Hospital used spatial multio-

The combined data uncovered spatial relationships between virus location

Genomics + proteomics “In the future, I’m looking

Pejman Mohammadi, PhD

Basic science researchers combining genomics + proteomics—Of researchers

MULTIOMICS RESEARCH EXAMPLE

Single-cell targeted resequencing + single-cell cell surface protein analysis

Tracking clonal evolution in myeloid cancers

Scientists at Memorial Sloan Kettering Cancer Center and the University

See how more scientists are using multiomics

Genomics + epigenetics + transcriptomics

Epigenetics + transcriptomics + proteomics

What’s next for multiomics