Genomics, Big Data and Diversity

Precision medicine based on genetic testing is far more accurate for Caucasians than for other groups. Tests can accurately determine a Caucasian’s risk for a range of diseases with a 10 percent false positive rate, which means the test detects a risk for a disease that is not present. For a Hispanics, the false positive rate is 60 percent. Such a disparity means that minorities are being left out of the major advances made by precision medicine in the detection and treatment of disease. In part, the disparity is because most medical research and clinical trials are conducted in Britain and America with Caucasian volunteers.

By combining the power of genomics, informatics, big data and artificial intelligence, David Craig, PhD, and John D. Carpten, PhD, co-directors of the Keck School of Medicine of USC’s Department of Translational Genomics, will hasten the day when everyone has access to accurate, personalized diagnoses and treatments for a range of conditions from cancer to Alzheimer’s disease. The department is uniquely situated to advance such research, given the rich racial and ethnic diversity of the individuals seen at the Los Angeles County + USC Medical Center.

“By investigating health disparities in terms of risk, severity and outcomes, everyone benefits,” Dr. Carpten said. “By diversifying study populations, we have a better chance of developing new and better ways to diagnose, treat and ultimately prevent diseases, including cancer, diabetes, hypertension and heart disease. Cancer management is now driven by this, so we can tailor treatment to that patient’s specific cancer. Unfortunately, most patients do not get that type of precision treatment. The goal is to try to make sure everyone has access to these approaches.”

A Unique Partnership

Dr. Carpten, an expert in genomics and health care disparities, and Dr. Craig, a biomedical engineer, make a unique team.

“We see different ways to approach a problem,” Dr. Carpten said. “David and I couldn’t be more different, so we each pick up things the other misses.”

Dr. Craig said, “John does a great job of communicating where the real need is. If I develop a hammer, then he figures out where best to use that hammer.”

Dr. Craig’s “hammers” are based on massive amounts of data.

“I’m a big data guy,” Dr. Craig said. “Every cell in the body has a genome that is 3 billion pieces of DNA long and there can be differences—we measure the differences. We boil down trillions of bytes of data into something meaningful, such as, if you have this mutation then this therapy will be the most effective – for you.”

Led by Drs. Carpten and Craig, department researchers are using their special tools for a range of projects, including:

• Dr. Carpten’s research into aggressive triple negative breast cancer, which has a high death rate, especially for African American women. He discovered a gene that makes chemotherapy ineffective, but also makes such tumors responsive to a specific therapy, thereby improving treatment for this hard-to-treat cancer. The Tower Cancer Research Foundation is funding this research.
• Identifying rare mutations in a subset of the Mexican population that greatly increase the risk of Alzheimer’s disease at age 40, which will provide insights into later-onset Alzheimer’s.
• Working with USC ophthalmologists and neurologists to identify biomarkers in tears that indicate Parkinson’s disease long before any symptoms appear.
• Collaborating with the Norris Comprehensive Cancer Center on the Oncology Research Information Exchange Network (ORIEN), a consortium of cancer centers collecting detailed molecular analyses of individual tumors and extensive clinical data to learn to identify aggressive tumors and determine which treatments are effective against which specific cancers.

Diversity is Key

The department seeks to increase the diversity of the participants in medical research, thereby increasing the accuracy of the results for all. Researchers also can see the proportions of various genetic ancestries in each person, which can spotlight genetic links to certain diseases and treatments. Elevated Native American ancestry may increase the risk for pediatric leukemia and decrease the effectiveness of chemotherapy, while higher West African ancestry may increase the risk for prostate cancer. Unfortunately, like most medical research, less than five percent of ORIEN’s 20,000 participants are Hispanic and/or Native American.

The department is leveraging a combination of research grade and clinical grade molecular profiling to help more people gain access to personalized medicine. UniHealth Foundation, which focuses on improving the health of underserved populations, is helping by supporting the research of the department. Jennifer Vanore, PhD, President and COO of UniHealth said, “Dr. Carpten and his colleagues focus specifically on underrepresented minority oncology patients, which will lead to critical advances in precision medicine.” UniHealth’s support allows the department to recruit 1,000 minority cancer patients, significantly expanding the minority representation in their research.

Drs. Carpten and Craig submitted a proposal to the National Cancer Institute’s Cancer Moon Shot program to focus specifically on 500 Hispanic/Latino colorectal cancer patients at LA County/USC Medical Center in their genomic research. The proposal earned one of the highest possible scores, but they have not yet heard a final decision about funding. If funded, the research will provide critical genomic information to the participants, which can be used to improve their care and treatment with more personalized approaches.

Sol Hamburg, MD, PhD, President of the Tower Cancer Research Foundation, recently welcomed Dr. Carpten to the foundation’s board, and said, “We support Dr. Carpten’s research because he and his team take full advantage of LA County+USC’s uniquely diverse patient population. His research program shows great promise to improve cancer care for everyone, including underserved minorities.”

Increasing Diversity Among Researchers

The department also seeks to increase diversity among researchers. The department was awarded a grant to create a Cancer Health Equity Center in partnership with the Norris Comprehensive Cancer Center, Florida A&M University—a historically black college—and the University of Florida. The partnership is researching health disparities in prostate, pancreatic and lung cancer. Dr. Carpten said, “We are growing the infrastructure at Florida A&M and training underrepresented minorities in this type of research, which is the foundation of precision medicine.”

The Future: Precision Medicine for All

For the future, Dr. Carpten said, “We want to explore new ways to assess the molecular framework of various diseases and democratize molecular profiling. I feel a sense of responsibility so that everyone has access to health care innovation and is involved in its development.”