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The Human Genome

Genome Sequencing

We are fascinated by the human genome. We have, for more than 10 years, built tools to interpret the genome in the context of health and disease. Specifically, we use the genome to solve rare diseases as part of the Undiagnosed Diseases Network and the Stanford Clinical Genomics Program. Through these programs, algorithms developed in the lab are rapidly applied to real patients (a recent example is our machine learning based indel caller).

We are excited by the potential of long read sequencing, which helps us understand complex areas of the genome. We work closely with the FDA and NIST to champion genome accuracy and develop strong quality metrics for the community. As well as rare disease, we are interested in preventive genomics and, in particular, the role of polygenic risk scores and pharmacogenomics in improving and individualizing patient care.

Sometimes, we take our ideas outside of Stanford via startups. We started Personalis (Nasdaq: PSNL) a cancer genomics company focused on immuno-oncology in 2012, and Deepcell a next generation diagnostics company combining tools from artificial intelligence and single cell genomics in 2018.

Genome Engineering

The advent of genome engineering technologies gives us the opportunity to edit the genome to study cardiac gene variants and potentially treat disease.

To study gene variants, we use CRISPR and similar tools to introduce libraries containing tens, hundreds, or thousands of gene variants into a heart muscle cell model. We then screen these cells for signs of cardiac disease, including changes to the structure and function of the cell, as well as changes in ion handling and gene expression. This can provide information about the impact of genetic variants even before they are seen in patients, improving diagnosis and treatment of cardiomyopathies.

We also believe that in the coming years, genome engineering will facilitate new targeted gene therapies for cardiomyopathy patients. Our previous work has shown that silencing the expression of RNA containing a cardiomyopathy-causing variant in mice showed partial restoration of healthy heart function and improved mortality. CRISPR and other genome engineering technologies will take us one step further, allowing us to precisely correct cardiomyopathy-causing variants in heart tissue, something we ultimately hope to bring into the clinic as a treatment for patients.