Next-generation sequencing is bringing precision medicine into the clinical realm

By Mike Miliard
05:03 pm

Genomic sequencing has come a long way in a short time, and its potential to drive even faster innovations in precision medicine is enormous.

To capitalize on that opportunity, however, health systems need data – lots of it, from all sorts of people. Kaiser Permanente has been building a biobank with genomic data and other health information from hundreds of thousands of patients from across its eight regions, and Nazneen Aziz, says it's already helping clinicians unlock insights into complex genetic challenges.

Aziz, executive director of Kaiser Permanente Research Bank, spoke during a HIMSS Learning Center webinar this past week, explaining the ways biobanks, with their data linked to electronic health record systems, are helping drive research discoveries at Kaiser and providing an opportunity for other health systems to collaborate.

A key catalyst for this innovation, of course, is the arrival of next-generation sequencing, which Aziz calls "the enabler of genomic medicine as it is today."

The Human Genome Project paved the way, and it seems hard to imagine a time, 13 years ago, when it cost $3 billion "just to get one human genome fully sequenced," she said. "Now, with next-generation sequencing, we're able to sequence individual genomes for under $1,000, and it's now come into the clinical realm."

Next-gen sequencing is "enabling large-scale scale sequencing very rapidly," said Aziz. And even in a U.S. healthcare system notoriously slow to adapt to change, it's being adopted fairly quickly, generating large volumes of increasingly complexity, from gene panels to whole exomes to whole genomes.

A challenge, however, is that "there is a big knowledge gap in clinical genomics," she said. "We know there are about 20,000 protein coding genes, and for about 5,000 of these genes we know their function — but we don't know the function of another 15,000 or so."

That, said Aziz, is "where population biobanks are critical."

More data from more people with more genomic profiles is essential if clinical researchers are going to be able to solve the mysteries — of which there are still many — of how genetics contribute to disease.

For instance, "we know that there are only about 667 validated drug targets," said Aziz. "And we know there are about 4,000 monogenic diseases, caused by mutation in a single gene."

But "while interpretation of protein-coding parts of the genome is somewhat mature, we still don't know how to interpret the parts that are in-between genes," she said. "Interpreting other parts of the genome is still in its infancy."

And recent years, for example, have revealed the importance of the intergenic region, DNA sequences between genes, which had previously been discounted or overlooked.

Indeed, the workings of monogenic diseases, caused by modifications in a single gene, such as sickle cell anemia or cystic fibrosis, versus complex or multi-genetic diseases (diabetes, obesity), which often develop in tandem with environmental or lifestyle factors, can be "hard for even physicians to understand sometimes," she said.

But the bigger and more diverse the data trove researchers can work with, the easier it is for them to arrive at genomic insights and develop new treatment strategies.

There are many biobanks around, the world, from the VA's Million Veteran Program, currently the largest in the world, to other large troves in the UK, China, Taiwan and Japan. But many biobanks are located at hospitals and health systems – not just at Kaiser Permanente, but Mayo Clinic, Geisinger Health System and more.

"Many hospitals are starting to do their own collection," said Aziz. "Now that the technology to sequence large numbers of patients has become so affordable and high-throughput, you are now able to connect the genomic sequence to the electronic health record and make great advances in understanding many diseases – not just the common ones, but also the rare ones."
Currently, Kaiser Permanente Research Bank is the second largest biobank in the U.S. (and the largest non-governmental biobank).

"About 5 percent of people in any healthcare system will be diagnosed to carry one or more of what are called clinically actionable diseases, meaning something can be done about their genetic variant and disease condition," said Aziz.
Many people have a genetic disease that has not been diagnosed and is not being managed properly because even the doctors don't know it's there.

"Through our biobank participant sequencing," she said, "we are able to identify the ones who have these undiagnosed disease and return it to the patient and the clinical care delivery site so it can be managed right." 

Aziz said the biobank program is open for collaboration with other healthcare institutions. You can learn more at the HIMSS Learning Center webinar: How Genomic Data Banks Are Enabling Progress in Precision Medicine.


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