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At the Lab Episode 26: The golden grail of genomics

image of Cold Spring Harbor campus from across the harbor with At the Lab podcast logo and portrait of Thomas Gingeras

First, there was the Human Genome Project. Then, there was ENCODE. CSHL Professor Thomas Gingeras recently spoke with Scientific American about the legacy of ENCODE. This week At the Lab, he talks about a new follow-up project called EN-TEx and its promise for the coming era of personalized medicine.

Thank you for joining us for the first season of our new podcast, At the Lab. If you missed any episodes, you can find them all in our podcast archive. Or tune in over the next few weeks, as we bring you a series of recaps from At the Lab Season 1.

Read the related story: Genome analysis just got personal


Transcript

Sam Diamond: You’re now At the Lab with Cold Spring Harbor Laboratory. I’m Sam Diamond, and this week At the Lab, “The golden grail of genomics.”

SD: The human reference genome is one of the greatest achievements of the modern scientific era. It pushed biology into the 21st century and revolutionized our understanding of genetics.

SD: But, at the end of the day, it’s just a reference—one genomic profile standing in for all of us. In reality, each of our genomes contains about 4.5 million genetic variants. Today, thanks in part to scientists who were involved in the Human Genome Project, it’s no longer cost-prohibitive to sequence any given individual’s genome.

SD: One such scientist is CSHL Professor Thomas Gingeras. After the Human Genome Project wrapped up, Gingeras became involved in a follow-up project called ENCODE. Short for the Encyclopedia of DNA Elements, this genomic database opened a world of possibility. Gingeras was quick to dive in, with EN-TEx.

Thomas Gingeras: This project started at the end of phase 3 of ENCODE. It was clear that more and more, individual genome sequences were going to be used in place of the reference human genome sequence. And the question then becomes what are the differences that you would see using the reference genome versus taking individual genome sequences, and then doing the same kind of analysis?

SD: If ENCODE was the sequel to the Human Genome Project, EN-TEx is the third installment in the trilogy. Gingeras launched EN-TEx alongside Yale Professor Mark Gerstein. Together, they led a team in profiling 30 tissues from four donors with 24 different genomic tests per tissue. As a result, they were able to compile a catalog of more than one million genomic variants—making it the most comprehensive per-genome resource of its kind.

SD: But they didn’t stop there. They also developed computational prediction models for evaluating each individual genetic variant in cases where collecting a tissue sample would be overly invasive, like if you’re looking into heart or brain conditions. How does Gingeras feel about all this?

TG: I think it’s quite exciting. I mean this [path leads us to a] golden grail that [scientists and physicians] have been wanting to do for a long time. And this is really the first attempt to provide a paradigm for getting to that goal.

SD: And it started right here At the Lab.

SD: Thanks again for joining us. If you like what you heard, please subscribe wherever you get your podcasts and visit us online at CSHL.edu. For Cold Spring Harbor Laboratory, I’m Sam Diamond, and I’ll see you next time At the Lab.