New tools take on an old disease

You are only as good as your tools.

In science and medicine, scientists have developed new tools to make sense of the avalanche of data they collect. Many of these tools have names ending in “omics.” For example, in the area of psoriatic disease, if you ask a scientist who has just received an NPF grant how she intends to achieve her project’s goal, she might tell you she’s going to use a technology called transcriptomics. Or genomics. Or epigenomics.

There are plenty more, many of them based on the study of DNA, RNA, proteins, metabolism and the microbiome. All of them may potentially provide clues to how diseases impact the body. This is the omics revolution: the invention of tools to help us make sense of the data analysis tidal wave.

With this knowledge, scientists hope to develop new approaches for managing complicated diseases like psoriasis and psoriatic arthritis (PsA), including:

  • Earlier diagnoses, long before inflammation can do its worst.
  • Personally targeted treatments tailored to a specific person's biomolecular factors. (This is also called personalized or precision medicine.)
  • More accurate predictions of how effective a particular treatment will be for a patient. 

Here are three ways in which the omics revolution is taking shape in psoriatic disease research.

Predicting comorbidities from your genome

Genomics seeks to identify abnormalities in your genome – your genetic material – that might cause disease.

Genomics technology uses a process called genome sequencing to examine your genome – the DNA that makes you the person you are. There are 3 billion pairs of letters that make up your DNA. Working from a blood sample, researchers can compare nearly all of those letters with a reference genome. Your susceptibility to a specific disease may be due to discrepancies between the two, to your unique combination of genes and how they’re expressed, or to other factors.

Alex Tsoi, Ph.D., is a researcher in the departments of dermatology, biostatistics, and computational medicine and bioinformatics at the University of Michigan. He received a 2018 NPF Discovery Grant to analyze data from volunteer health records using genomics. This task may sound straightforward, but it’s not. Tsoi must make sense of information about many different patients recorded by many different clinicians.

Tsoi’s goal is to identify other diseases that appear among people with psoriasis, their frequency and their possible genetic cause. This includes disorders that doctors might not currently associate with psoriasis.

“The most exciting part is to understand if we can use genetic data alone to figure out if patients are prone to other diseases,” he says. “Identifying comorbidities and the genetic components they share with psoriasis is critical for understanding their common biological mechanisms.”

Examining clues in gene expression

Inside the cell, the eventual use for most of the genes in our DNA is to create different proteins that do specific jobs at specific times. Genes provide the code to create the proteins. This process is called gene expression. Epigenomics is the study of the structure of long strands of DNA molecules and how that structure, and components that impact the structure, affect gene expression, including the production of cytokines, a pro-inflammatory protein involved in psoriatic disease. The genes are transcribed to RNA and then through complex cellular processes, the RNA is translated into a variety of specific proteins.

Johann Gudjonsson, M.D., Ph.D, is a member of the NPF medical board, an associate professor of dermatology at the University of Michigan, and a recipient of a 2012 NPF Translational Grant. His research currently focuses on why so many patients experience psoriatic disease – and respond to psoriatic disease treatments – so differently.

His latest study explores these topics using data from more than 1,000 people living with and without psoriasis. Gudjonsson and his team are using epigenomics and transcriptomics to examine gene expression in individual cells as the cells react to treatments.

“Epigenomics has helped us understand a lot. But we are barely scratching the surface,” Gudjonsson says. He believes that once researchers learn how to mine the data for an answer, a simple blood test or skin biopsy might someday paint a comprehensive picture of someone’s
disease, leading to a more effective way to treat it.

“It’s important to ask ourselves how we’re going to analyze and integrate the different omics data into something that makes biological sense,” he says. “For me, the biggest change [with omics] has been that you can take a global view of what’s going on in the cell and form a hypothesis from there.”

Warning flags in the blood

The creation of a protein within a cell begins with a message from the genome to the cells. This message is called an RNA transcript. It’s something like the script actors use to learn their lines. The cells search the transcript for their specific message. Transcriptomics is the study of how these messages move within the cell, including how the messages were created, how they are read, and what functions they are asking the cell to perform. Transcriptomics can tell us whether a cell is doing what we think it should be doing. Have the genes been messaged accidentally, producing proteins that lead to inflammation? Is a cell responding to a biologic the way it should be responding? Transcriptomics can help scientists piece together the different steps that cause cells to misbehave.

Lihi Eder, M.D., Ph.D., is a researcher on the staff of the Women’s College Research Institute of Toronto, Canada. Eder, a recipient of a 2018 NPF Discovery Grant, is merging omics technology with medical imaging to get at the heart of why many patients with PsA don’t respond to treatments, or don’t respond as expected.

Eder and her team use ultrasound and MRI imaging to identify and characterize different varieties of PsA. She then plans to perform a transcriptomics analysis on the patients’ blood to find biological markers, or warning flags, that correspond to these different PsA subtypes.

“Everybody is talking about personalized or precision medicine,” she says. “The model we’re developing could be the first step towards a personalized medicine approach in patients with psoriatic arthritis.”

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