Bringing Precision Medicine to the Developing World

“Precision medicine” is a relatively new term for a concept that has been part of health care for a long time. When you need a blood transfusion, for example, your donor’s blood type is carefully screened and matched to yours. That’s precision medicine.

Modern precision medicine goes well beyond matching blood types, considering gene variability, environment, and lifestyle for each person, so that clinicians and researchers can accurately predict which strategies and treatments work best for which people.

One of  the most promising approaches to precision medicine in the genomics era involves the study of how genetic makeup affects an individual’s response to drugs – pharmacogenomics. Knowing the genetic variant-to-drug response interactions of a patient provides a path to optimum individual treatments, maximizing drug efficacy while minimizing adverse reactions.

“We respond to medication in different ways depending on our own unique genetic profile; that is, the sequence of our genome has a lot to say about our health and how we will be treated in the precision medicine paradigm,” says King Jordan, professor in the School of Biological Sciences at the Georgia Institute of Technology, where he directs the Bioinformatics Graduate Program.

“The idea here in the developed world with respect to precision medicine is that you take into account each individual’s genetic code when we make decisions about their healthcare,” continues Jordan, who is also a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

“It has tremendous potential, owing to the technological revolution in genome sequencing – now it’s much faster and more cost effective to sequence all of your individual genomes and use that data to inform those healthcare decisions. Unfortunately, that approach is still prohibitively costly and out of reach for the developing world.”

With that in mind, Jordan and colleagues at Georgia Tech have been collaborating with researchers in Colombia on a more feasible, broad-based approach, a concept called precision public health.

“The idea is to allow for the technological developments of precision medicine to make their way into the developing world. We’re trying to change the way precision medicine is done,” says Jordan, whose work is explained in a research paper he and his collaborators published earlier this spring in the journal Frontiers in Genetics.

“We use a population level focus, to help ensure that resources are allocated where they will yield the most return on investment. That’s the idea of precision public health,” Jordan says. “So the focus is not on individual patients not initially. It’s on populations, and instead of doing cost prohibitive characterization of every individual patient’s genome, we’re characterizing the sequences of a sample of individuals from a population.”

The work seeks to address global health disparities by bringing advanced bioinformatics technology and genomic research to Colombia, and adheres to Georgia Tech’s strategic mission, specifically Goal 4: “Expand our global footprint and influence.”

The paper, entitled, “Population Pharmacogenomics for Precision Public Health in Colombia,” is a collaboration between Jordan’s lab at Georgia Tech, and a team of researchers from Colombia, including Juan Esteban Gallo, a former Fulbright Scholar under Jordan’s guidance at Tech, and now an associate professor at CES University and scientific director of GenomaCES Biotechnologies in Medellin (Antioquia).

GenomaCES is Colombia’s first clinical genomics laboratory, a company spun out of the university currently working to develop genomic diagnostic aids and treatments, based on next generation sequencing technologies. Other collaborators include the Universidad Tecnológica del Chocó, and the Biomedical Research Institute in Cali, Colombia.

“Our research focused on two neighboring regions with distinct ancestry profiles,” explains the paper’s lead author, Shashwat Deepali Nagar, a Bioinformatics graduate student in Jordan’s lab. “Antioquia and Chocó.”

These disparate groups in Colombia, with an assist from Georgia Tech, have joined forces to understand their differences at a genomic level so that they can develop cost-effective and rapid pharmacogenomic assays, which can be efficiently deployed in resource-limited settings.

People in Antioquia have primarily European genetic ancestry, followed by Native American and African components, while people Chocó show mostly African ancestry, with lower levels of Native American and European traces. The researchers performed a survey of the global distribution of pharmacogenomic variants, and a more tightly focused study of differences between the two different Colombian populations.

“What we expected and hypothesized to see in these two states with distinct ancestry profiles, are genetic variants found at different frequencies,” Jordan says. “If those variants mediate how individuals react to certain drugs, then one might expect a different profile of drug reactions in the two populations. That’s where the population pharmacogenomics comes in.”

The basic idea is to interrogate the frequency of these pharmacogenomic variants in the two populations and use that data to inform healthcare decisions in Colombia, “so they can adopt best practices of precision medicine in a cost effective way,” Jordan says.

The work required some deep data mining, as the researchers dug in the Pharmacogenomic Knowledgebase (PharmGKB) for human genetic variants with specific drug responses. One example of an important drug reaction, relevant to the populations that were part of the study, is related to one of the most prescribed medicines in the world, statins (cholesterol lowering drugs).

The researchers developed an assay to test regional anecdotal knowledge: In Antioquia, physicians had noticed adverse reactions in more than 30 percent of their patients, but they had no idea why this was happening. The new assay demonstrated that 33 percent of individuals in Antioquia are predicted to have an adverse reaction based on their genetics.

“So our collaborators in Colombia leveraged that information to build a specific, local, in-house genotyping assay, which they can run at a very low cost, to predict adverse reactions to statins” says Jordan, who has worked for many years with collaborators in Colombia, which all started as an effort to build capacity in bioinformatics and genomics. “We’re particularly excited about this latest work because it truly is the most translational research my lab has done so far, with the potential to make a direct and tangible impact on public health in a vibrant, developing country.”

Georgia Tech’s work in Colombia continues this summer when Nagar heads back to Medellin to work with his colleagues at GenomaCES, developing a computational platform to integrate genomic information with clinical data taken from electronic health records, the idea, again being, “to help translate the best practices in precision medicine from the U.S. in a way that is cost effective and applicable to the on-ground conditions in Colombia.”