In the not-so-distant future, whole-genome sequencing — determining a patient's entire unique DNA makeup in the laboratory — will be as routine as X-rays and cholesterol testing. The challenge, though, is accurately interpreting the vast amount of data generated by genomic sequencing and effectively using it to guide decisions about health care.
The goal of the Mayo Clinic Center for Individualized Medicine's Clinomics Program is to speed up translation of personalized medicine discovery science to individualized patient care. The program builds on Mayo Clinic's culture of collaboration and research to create and refine evidence-based tests and treatments and bring them to patients faster.
The Clinomics Program is increasingly grounded in and driven by implementation science — research on how to advance and accelerate the introduction of new, evidence-based ideas and approaches into patient care. By looking at real-world factors that impact care and developing and refining methods to better share and use new knowledge, implementation scientists in the Clinomics Program ensure that proven individualized medicine breakthroughs become available to as many patients as possible, as fast as possible.
With these new tools in hand, doctors will be able to search patients' genetic codes quickly and effectively to find clues to help diagnose and optimally treat patients' conditions — or keep them healthy by preventing future disease.
To make these advances, clinicians and scientists collaborate with bioinformatics and information technology experts, hastening the translation of discoveries from the bench to the bedside. Multidisciplinary research teams integrate genomic data into clinical systems — such as electronic health records (EHRs) — and create new tools that enable doctors to access, visualize and use genomic information in patient care.
The Clinomics Program includes individualized medicine patient care across Mayo Clinic, ongoing translational research projects, and the creation and expansion of systems for future integration of multiomic data — such as transcriptomics, exposomics and metabolomics — into clinical practice.
Individualized medicine in patient care
Mayo Clinic's individualized medicine patient care team uses DNA sequencing to advance the science of precision medicine while translating discoveries into faster diagnoses and more effective treatments for patients.
At Mayo Clinic, physicians, genetic counselors, laboratorians, bioinformaticians and bioethicists work together to solve unique and challenging cases and provide cutting-edge care.
Mayo Clinic today offers four individualized medicine services for patients.
For patients who have cancer, whole-exome sequencing of normal DNA and tumor DNA may identify genetic changes (mutations) that are causing or expanding the cancer. Clinicians may then be able to use that information to find personalized treatments that can target those mutations.
The Center for Individualized Medicine's groundbreaking Interrogating Cancer Etiology Using Proactive Genetic Testing (INTERCEPT) study found that roughly 10% to 25% of the genetic mutations that can lead to cancer are inherited mutations, and that 1 in 8 patients with cancer had an inherited cancer-related gene mutation — much higher percentages than previously estimated. The Clinomics Program is now leading efforts to incorporate findings from the INTERCEPT study into cancer care across Mayo Clinic.
Genomic sequencing also creates the possibility for patients to share the heritable cause of their cancer with their relatives, allowing family members to pursue care for earlier detection and, if necessary, management or treatment.
Individualized Medicine — Holly's Story
Sequencing uncovers the genetic makeup of an aggressive tumor.
Rare and undiagnosed diseases
These services are for patients who have a rare genetic condition or have a possible genetic condition but still have not received a clear diagnosis. These patients are sometimes known as "diagnostic odyssey" cases.
This includes patients with an early-onset disease or a syndromic disease of unknown etiology, as well as those whose family history suggests their condition is inherited. Genetic sequencing may be used to discover the genetic alterations that contribute to disease development, may influence treatment or both.
The Clinomics Program leads Mayo Clinic's implementation of genomic testing into clinical practice to better assess disease outcomes and enhance research and treatment opportunities for patients with rare diseases. Building on Mayo Clinic's tradition of offering premier medical diagnostics and treatment, these services give patients and clinicians information to better diagnose rare genetic diseases and, in many cases, provide targeted therapies.
Individualized Medicine — Dustin's Story
Genome sequencing provides a diagnosis for a rare neurological disorder.
Genetic Testing's Impact on Patient Care — Paige's Story
Whole-exome sequencing probes into a young patient's bone and joint pain.
The Clinomics Program is focused on bringing the science of pharmacogenomics — the study of how genes affect the body's response to medications — into clinical practice so clinicians can use genetic information to find the right drug for the right patient at the right dose.
Successful implementation of this new specialty requires a robust, multifaceted education effort across the enterprise. The Clinomics Program provides health care team education and trains Mayo Clinic pharmacists to support clinicians by reviewing genetic test results and recommending medications that will give the best results with the fewest possible side effects.
To advance clinical use of pharmacogenomics, the Center for Individualized Medicine's RIGHT 10K Study sequenced more than 10,000 Mayo Clinic Biobank participants and embedded the resulting data in the patients' EHRs. Clinicians treating these patients can now act on information with guidance from a pharmacogenomic best practice alert system developed at Mayo Clinic.
Pharmacogenomic Testing — Karen's Story
Pharmacogenomic testing helps a patient and her family members find answers to health-related questions.
Individualized Medicine — Andrew's Story
Applied pharmacogenomics resolves a patient's lifelong anxiety and depression.
Mayo Clinic research has found that predictive genomic testing — testing that looks for genetic mutations in otherwise healthy people — may identify hereditary risks in nearly 12% of people tested, who may therefore benefit from preventive care. Predictive genomics services are already offered through Mayo Clinic's Executive Health Program and Predictive Genomics Clinic. Ongoing research aims to expand these services to reach larger and more diverse populations.
The Tapestry DNA Sequencing Research Study is a large-scale study actively engaging Mayo Clinic patients to understand the role preemptive genetic testing plays in predicting and preventing an inherited form of high cholesterol called familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome — a form of hereditary colorectal cancer.
Additionally, researchers from Arizona State University, Mayo Clinic and Mountain Park Health Center collaborated on the Return of Actionable Variants Empirical (RAVE) Study, which brought genomic medicine to low-income patients in the Phoenix area. As part of the study, 500 Latino adults consented to have their DNA sequenced for genes that predispose people to diseases such as heart disease and breast and colon cancers. Then, the results were shared with the participants and their health care providers for follow-up.
As well as providing participants with valuable information about their health, the study helped researchers assess the feasibility of offering genomic screening in a nontraditional setting. Researchers are now extending this work through the Electronic Medical Records and Genomics (eMERGE) Network, consortium of U.S. medical research institutions that is organized and funded by the National Institutes of Health.
Through translational research on cancer screening, rare genetic diseases, pharmacogenomics and predictive genetic testing, the Clinomics Program advances the science of individualized medicine and finds ways to implement discoveries and new best practices in patient care faster and more effectively.
Whole-exome sequencing data analysis
Many questions remain about how whole-exome sequencing is best used in patient care. To begin answering them, the Clinomics Program conducts many projects that analyze whole-exome sequencing data from Mayo Clinic Biobank samples.
As is being shown through individualized medicine care at Mayo Clinic, analysis of these data will continue to improve how investigators:
- Determine which variants and findings are clinically relevant and actionable
- Share results concisely and effectively with clinicians and patients
- Address bioethical considerations as they arise
The data are also being used to compare different genomics sequencing approaches and determine which are most suitable for optimized clinical use, implementation and value. Additionally, data analysis allows for the creation of better online resources and tools for clinicians — such as best practice alerts in the EHR — as well as improved data management and standardization.
Ethical research and care
We know that genomic information is very personal — as is any part of an individual's medical record. This is evidenced by the trust expressed over the years by Mayo Clinic patients. Mayo Clinic takes that trust very seriously.
In that tradition of respect and trust, the Center for Individualized Medicine — through integrated teams of bioethicists, medical geneticists, physicians, genetic counselors and other specialists — develops procedures and rules to protect patients' rights and uphold the highest level of ethical diligence in research and care.
The Clinomics Program considers and accounts for issues including:
- Patient privacy. Each area of the Center for Individualized Medicine includes regulations and procedures for protecting information and patient privacy. Specific safeguards and informed consent may be customized to fit the processes of each area, but all encompass protection for the individual patient.
- Insurance. Mayo Clinic does not release any genomic information to patients' insurance providers without consent from the patient.
- Information security. Mayo Clinic protects patient information and every electronic medical record with multiple levels of security, including all genomic information. We do not and will not share any information without explicit and informed consent from the individual patient or study participant.
- Genomics in research. The consent processes required for genomic research are different from those for patient care. Sharing of genomic research information often involves collaborators at Mayo Clinic and other institutions, but only with appropriate permissions from the participant. Permissible and appropriate access by staff to medical records is clearly documented, with compliance auditing and reporting as required.
- Bioethics and community involvement. The center's Community Advisory Board of informed and interested citizens, as well as its Bioethics Program, oversee research and consider complex ethical questions to arrive at the best practices in genomic medicine and research.
Patients, research participants or members of the public are welcome to ask questions about any aspect of this new approach to medicine.
Clinomics quickly moves discoveries from the research lab to the clinical setting, with practical, cost-efficient genomic tests for diagnosing and treating patients.