Dr. Margulies is no stranger to Children’s. He was the hospital’s first Chief Information Officer from 1986 to 1990, and went on to launch several successfully acquired companies. In 2001, he and other colleagues from Children’s created Correlagen Diagnostics (now a part of LabCorp), where he led the development of automated genetic testing systems. Now he has returned to Children’s, bringing his academic and commercial experience and success to bear in the service of the GP.
TIDO: What does the future state of medicine look like, and how will the Gene Partnership help us get there?
Dr. Margulies: The systems biologist Leroy Hood has described the future of medicine as “predictive, preventive, personalized and participatory.” It is based on a clearer understanding of the interactions of complex elements that underpin health and disease. This future systems biomedicine hopes to explain the impact of genetic variation along with environment. In practice, we may be able to understand the behavior of a specific cancer and use this information to choose more effective treatments. In short, we should be able to characterize a patient’s expected response to drugs and many uncommon illnesses may, finally, be understood and treated.
The Gene Partnership is assembling the basic tools and methods of systems biology, creating new ones, and setting out a blueprint to apply them to both research and the practice of pediatric medicine at Children’s.
TIDO: What is the overarching goal of the Gene Partnership?
Dr. Margulies: The ultimate goal of the GP is to better understand the role of genomic measurements in understanding disease and creating precision treatments for individuals. Over time, we are building a large cohort of patients and families and analyzing both genomic and phenotypic data to uncover meaningful insights about the root causes of disease. While we build critical mass toward that goal, we will also utilize the infrastructure and methods that power the Gene Partnership to bring immediate benefits to patients and the research community.
TIDO: What is the Gene Partnership’s structural and process blueprint?
Dr. Margulies: The GP is focused on obtaining extensive genomic data (DNA sequence, RNA sequence, and epigenetic measurements) from large numbers of consented patients and family members with well-characterized disease phenotypes and electronic medical record (EMR) data. We will seek to correlate genome-derived and phenotypic measurements with other known data to evaluate specific research hypotheses, and will use the findings to diagnose and guide treatment decisions. Finally, we will also use advanced bioinformatic techniques for non-hypothesis driven exploration of this copious data set.
All of this work is taking place in the context of a revised collaborative arrangement between families, patients and researchers in which patients are informed in real time of advances in knowledge related to their genetic profile.
TIDO: What will the GP do in the short term?
Dr. Margulies: In the early years, the Gene Partnership will focus on several specific clinical and research projects: safer use of prescription medications, selection of cancer chemotherapy regimens most attuned to the specific state of an individual’s cancer, genomic sequence-based definition of previously undiagnosed serious illnesses in children, and pilot multimodal assessment of children with autism spectrum disorders.
This is just the beginning, as a number of other projects are in the early planning stages. In each project, the Gene Partnership team will address consenting, phenotyping, specimen collection, genomic analysis and interpretation. All will be done in a manner that advances the specifications and features of Gene Partnership methods and systems for use on other projects.
TIDO: What opportunity does collaborating with the Gene Partnership represent for partners outside of Children’s?
Dr. Margulies: The infrastructure we are building will be a powerful generator of new knowledge. Because it is based on detailed data from a large population – data that can be navigated in a way that protects patient privacy at both the macro and micro levels – it represents opportunities for collaborators of all types in academia, government and industry. On the therapeutic development side, the tools will be useful for stratifying patients for clinical trials, performing in silico phase IV clinical studies, quickly identifying adverse events and finding relevant biomarkers. For diagnostics, the practice of large-scale medical genomics will not only identify new genes and rare variants associated with disease, but also uncover unique combinations of gene variants associated with more subtle phenotypes and suggest which treatment options would be more or less appropriate.
All of our data will build upon and add to the bodies of genomic data currently available to the public, as we fully recognize that the true power of genomics lies in the aggregation of data from extremely large populations. Children’s now has the pieces in place to obtain, analyze and report these data for the benefit of patients.
- CLARITY Contest Website
- The Gene Partnership Video
- The Wall Street Journal features the Gene Partnership