Approximately 3 years ago, we held a clinical bioinformatics summit to discuss with international leaders in genomics, genetic testing and clinical laboratory procedures what it would take achieve clinical grade whole genome sequencing (WGS). That is to make WGS a safe and useful component of routine diagnostic assessments in the clinic. Among the mechanisms we chose to accelerate the advent of clinical grade WGS was a competition where 3 families contributed their genomic sequence and clinical histories. Then multiple teams assembled and competed to produce the most accurate, most clinically useful diagnostic report. The competition resulted in a lot of learning and multidisciplinary team formation but also, even though we had not dared count on it, several breakthrough diagnoses. A good lay summary can be found here from Bio-IT World and an in-depth scientific summary here. Also, the cake presented by one of the mother’s to her child, who had gone for years without a diagnosis until the leading teams converged on the same mutations in the same gene, is shown below. With generous funding from Rob and Karen Hale, we kicked off the next round of the CLARITY competition as described below.
In addition to rare undiagnosed diseases, perhaps the most clinically impactful area of genomics, in the near term, is that of precision diagnostics for cancer. However, the analytic challenge is far deeper as it requires analyzing tumors that are often heterogeneous (i.e. different clones), comparing it to germ line sequence (i.e. non-tumor DNA). Then, how are we to determine which of the mutations found are relevant to the diagnosis or therapy selection? Integrating information from RNA sequence and epigenetic modifications (e.g. DNA methylation) may help and there are several good ideas being proffered by several researchers. Yet, how do we begin to bring all the data together systematically and meaningfully for patients with a malignancy? Given how early we are in this new realm of medicine, we decided to first hold a workshop where several national leaders in cancer genomics gave thoughtful assessments of the best way forward. After we we synthesize the learning from this meeting, we will announce a new CLARITY challenge for patients with recurrent cancers. Shown below are some of the speakers at the meeting which included Gad Getz, Rick Wilson, Peter Park, David Sweetser, David Margulies, Isaac Kohane, Judy Garber, Sharon Plon, Steve Chanock, Marian Harris, Heidi Rehm, Levy Garraway, and Katie Janeway. Another small but important step forward in the development of a data-driven, computationally-enabled medicine.