Genome Sequencing Crucial for Precision Medicine


Fully understanding a patient's genes may help physicians treat rheumatic diseases.

Genome sequencing may be fundamental to eventually offering precision medicine to patients with rheumatoid disease, but it will only reveal part of the patient’s health story, said Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York.

To get a full picture of a person’s disease outlook, researchers must deploy the latest technologies in epigenetics, metabolics, and the microbiome to understand environmental impacts on the immune system, Menschel said. Such tools are beginning to allow researchers to identify rheumatoid diseases early, before cumulative damage has occurred, and perhaps determine which patients will benefit from emerging targeted therapies, she said during a discussion at American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals Annual Meeting

(ACR/ARHP) Annual Meeting 2017, held here recently.

“Are we closer than we think? I think so, but we are still far away and scratching the surface,” Pascual said. “The good news is that there are many more layers…and the number of technologies that we can apply is unbelievable and will generate tremendously useful data. Now the challenge is to truly integrate that data in ways that will help us clinicians.”

Fortunately, the basic high-throughput tools that support precision medicine are improving every day, such as those for the study of epigenetics, she said. Technological advances now make small samples of cells, and even single cells, amendable to study that can provide tremendous insights, she said.

Gene expression profiling, proteomics tools, and antibody profiling are all also playing an important role in the understanding of rheumatoid disease, which will lead to improved diagnosis, disease stratification, clinical trial design and, ultimately, therapies, she said.

“This is a very exciting time to look at human disease,” Pascual said.

Research in systemic lupus erythematosus (SLE) is one disease in which precision medicine technology is helping research, though it has not yet translated to the clinic, she said. Only one new drug has been approved for lupus in more than 60 years, she said.

The heterogeneity of the disease is a big challenge, she said, sharing a genetic mapping study of 27,000 lupus patients that illustrated its genetic complexity. How might a clinical trial be designed to deal with such complexity?

Pascual highlighted work her team started years ago at a pediatric rheumatology clinic in North Texas, in which they collected data on and tracked all patients with lupus. The team analyzed genetic expression, identifying genes that were low when disease activity was low and high when the patient was doing worse. They looked at gene expression that was not impacted by ethnicity and certain treatment, hoping to identify relatively robust, reproducible transcription biomarkers.

The analysis indicated different biomarkers could work for different patient groups. For instance, in African-American patients, plasmablasts were very robust biomarkers, which could have implications in selecting targets and designing clinical trials, she said.

Two members of Pascual’s team dug into the heterogeneity by not putting any patient in a group or classification. In every patient, they found a set of genes that tracked with every single disease flare-up.

When examined collectively, they found 5 major biological pathways corresponded with all of these genes. Though the expression of the genes didn’t correlate in all of the patients, this indicates a potential area for further study, she said.


Pascual MV. Precision Medicine for Rheumatic Disease: Closer Than You Think? Presented at: 2017 ACR/ARHP Annual Meeting; November 3-8, 2017; San Diego.

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