Matthew Lebo: Tools for Clinical Interpretations
Director of Bioinformatics and Assistant Laboratory Director, Genome Sequencing
Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine
Recommended by Heidi Rehm, Laboratory for Molecular Medicine Partners Healthcare Center for Personalized Genetic Medicine
Matthew Lebo lives in two worlds, that of bioinformatics and computational biology and that of a clinical geneticist. At Harvard's Laboratory for Molecular Medicine, he then naturally fit into leading up its effort to launch genome and exome sequencing as a clinical service.
Currently, Lebo said, they have a low level of clinical samples coming through their lab. Most of what they are focused on is supporting the MedSeq project headed by Robert Green that is examining the role of genome sequencing in the clinic through a randomized, controlled study. Lebo and his colleagues are tasked with analyzing and interpreting those genomes.
The study is drawing upon both healthy people who are enrolled through their primary care physicians and people with cardiomyopathy who are enrolled through their cardiologists. They are then randomly assigned to receive the standard of care or that standard plus genome sequencing.
For the people with disease, Lebo and his colleagues are examining the genome looking for variants linked to the disease. They are also returning a broad list of incidental findings from the medical exome to the patients' physicians. In addition, as part of the MedSeq study, they are working to develop a cardiac risk profile through a more genome-wide association study-based approach.
"Our general clinical service will include the primary indication report and this broader incidental findings report," Lebo noted. The incidental findings they report back is broader than those recommended by the American College of Medical Genetics and Genomics, he added.
The variant assessment process can be time-consuming, Lebo said, and depending on the level of information available, it can take hours. And now as they sequence more and more people, it is becoming more difficult to reduce that amount of time.
"As we jump to genomes and exomes and really larger panels, we're coming across, obviously, a lot more variants that we need review of, but also we're coming across variants in genes that we are less familiar with," he said. "So there is an extra component now for our variant assessment process that wasn't there before."
Community efforts like ClinVar, which houses information about variants and their links to human health, will be valuable in making this process easier, Lebo said.
"Obviously no one can be expert in every single disease and so being able to use the broader community to aid in the interpretations is going to be tremendously valuable both for us and for the patients," he added.
Paper of note
Earlier this year, Lebo and his colleagues published a paper in Clinical Genetics outlining their variant assessment process. As they reported in their paper, they start by searching the literature and other databases for data and draw on statistical analyses of variants in the general population as well as computational predictions of the impact of those variants. They then weigh those lines of evidence to determine the potential that those variants can cause disease.
In the future, Lebo said that genomic information would play a larger and more integrated role in the clinic. For instance, he said that people's genome sequences could be stored in their electronic medical record, and as new issues arise in the patients or new knowledge about the variants they have is uncovered, clinicians could use that to better treat them.
And the Nobel goes to…
If the Nobel committee were to give him a call, Lebo would like it to be for "having created a robust infrastructure for appropriately using genetics in a clinical context," he said.