FOR PHARMA &
LIFE SCIENCES
CUSTOMER STORY
Pathway Diagrams Offer a New
Paradigm for Disease Research
ExECUTivE SUMMaRY
As our understanding of disease biology expands, the ability
to review all the current information on a particular disease or
organism in one place becomes critical. Dr. Victoria Petri at
the Medical College of Wisconsin has created the Rat Genome
Database as one such online resource for researchers. Elsevier’s
Pathway Studio plays a critical role in making that data accessible
through the creation of customized pathway diagrams that help
researchers visualize and connect to a wide variety of biological
data and resources.
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FOR PHARMA & LIFE SCIENCES
As medical researchers increasingly
pursue network-centric approaches
to understanding diseases and their
responses to drugs, the ability to
visualize metabolic, signaling and
regulatory pathways has become a crucial
navigational tool. Research scientist Dr.
Victoria Petri has been hard at work for
more than a decade building one of the
most accessible and thorough collections
of these tools to help those researchers:
the Pathway Portal for the Rat Genome
Database (RGD).
The Medical College of Wisconsin’s
Human & Molecular Genetics Center
hosts the free online RGD database, which
contains nearly 4.5 million functional data
annotations for rat, human and mouse
genes, and information on 500,000
disease-specific annotations. Since 2007,
Dr. Petri’s use of Elsevier’s Pathway Studio
to create reference pathway diagrams for
disease and altered pathways, associated
drug pathways, pathway suites and suite
networks has been enriching the database
content for all who use it.
In a paper published in Human
Genomics in 2014, Dr. Petri and her
colleagues described the Pathway Portal
as “a rich resource that offers a range
of pathway data and visualization,
including disease pathways and related
pathway suites.” Besides contributing
to fundamental research, the Pathway
Portal demonstrates the value of
visualization in the network-centric
approach to understanding the
molecular mechanisms of disease.
“We initially developed a resource
dedicated to pathways for use in
annotating the Rat Genome Database,”
says Dr. Petri, “and I thought it would
be nice to have visualizations for the
annotations.” She says it wasn’t just
graphics that made Pathway Studio
appealing for achieving that. “The
Pathway Studio database allowed us to
link users to gene report pages via the
RGD:ID the database provides, among
the many data types available for the
objects it contains. It also allowed us to
offer additional information via links to
pathway and small molecule ontology
report pages and to lists of objects,
through attributes and their associated
values that we can add to the database.”
Her team has now contributed almost
200 diagrams and continues to add
new ones to the Pathway Portal at the
rate of about one plus per month. The
images have attracted many more users
to RGD, she says, because “it’s one thing
to see a list of genes; it’s a completely
different thing to see how they connect
to one another.” To understand molecular
mechanisms of systems biology it is
necessary not just “to define the function
of a gene, but to identify the context
within which gene functions act,” she
and colleagues explained in Human
Genomics. “It is within the network, or
pathway context, that the function of a
gene fulfills its ultimate biological role.”
CUSTOMER STORY: Pathway Diagrams Offer a New Paradigm for Disease Research
“The Pathway Studio database allowed us to link users to gene
report pages and more, and it’s also a great tool for creating pathway
graphics, which are an essential component of the interactive pages
we create. Users can study the pathways by species, and you can
navigate from pathway to pathway to explore the network landscape.”
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FOR PHARMA & LIFE SCIENCES
For instance, in the same publication,
Dr. Petri and colleagues presented
diagrams of several collections of altered
pathways associated with diseases such
as pancreatic cancer, prostate cancer
and renal cell cancer, as well as diagrams
showing normal and altered pathways
for hypoxia inducible factor, the folate
cycle metabolic pathway, an estrogen
pathway suite, and a pathway suite for
methionine, homocysteine, folate and
related metabolites. Each diagram
of an altered pathway in the Pathway
Portal can be compared with a view
of the normal pathway. “An altered
pathway and the diseases in which it
is manifested shows the culprit genes
color-coded, with affected connections
removed,” she explains. “Annotations to
pathway ontology terms are made across
human, mouse and rat genes to broaden
their usefulness.”
Dr. Petri says she builds every pathway
diagram manually, adds attributes such as
pathway ontology IDs to the database and
assigns values. By saving the diagrams in
HTML, every element of each pathway
she adds contains linkable information for
the researcher, and every object depicted
in a diagram links to deeper information,
such as gene report pages, orthologs,
pathway ontology report pages, or lists
of genes, with links within, created with
a content management system (CMS)
and whose URL has been added to
Pathway Studio database. The work
thereby creates in-depth views of
annotated genes. The ability to easily edit
any aspect of a pathway diagram is unique
to Pathway Studio.
Explains Dr. Petri: “We create the diagram
and the web application RGD developed
to create the diagram page pulls data
from the database for the genes that
have been associated with the pathway,
their connections to other pathways,
diseases or phenotype, uploads the
diagram, and allows for other elements
to be added. Viewers can study the
pathways separately by individual species
(human, mouse or rat) and the ontology
we developed—a navigational tool
unavailable anywhere else—lets you
go from pathway to pathway and travel
the network landscape.”
As Dr. Petri and her colleagues conclude
in their Human Genomics paper:
“Having access to a large collection of
disease and associated altered pathways
enables the user to quickly inspect,
compare and identify aspects that may be
unique or aspects that may be intriguing.
As such, it can prompt asking new
questions or redefining previous ones,
lead to the search for new or revised
venues of inquiry, and overall help further
the efforts aimed at deciphering the
mechanisms that determine the initiation
and progression of disease.” And, indeed,
Dr. Petri says that Google Analytics data
about the use of the Pathway Portal
indicates that researchers from industry
and academia all over the world are
benefiting from her team’s hard work.
In 2014 alone, more than 180,000
users in 190 countries accessed the
16-year-old $35 million online resource,
and in early 2015 the RGD was awarded
a four-year $8 million NHLBI grant for
continued development.
CUSTOMER STORY: Pathway Diagrams Offer a New Paradigm for Disease Research
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