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Pathway Diagrams Offer a New 

Paradigm for Disease Research


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.




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.”




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

Pathway Studio® trademarks are owned and protected by Reed Elsevier Properties SA, used under license.


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