Mining the Genome with Dr. Bruce Korf

Mining the Genome - Issue 2 / All of Us Research Program Update

Mining the Genome - Issue 2 / All of Us Research Program Update

We’re wrapping up November with our second “Mining the Genome” conversation with Dr. Bruce Korf, CCTS Genomic Medicine Director. Over the course of the month, we’ve introduced our members to the newly launched All of Us Researcher Workbench beta, and in this conversation, Dr. Korf helped provide some quick takeaways for utilizing this resource:

  • UAB is the hub of the All of Us Southern Network, strengthened by the CCTS Partner Network, and was one of the largest enrolling sites in the country before the current pandemic.

  • Reactivation efforts are underway, with emphasis on participant retention, including re-consenting participants to utilize the now-available genome sequencing and genotyping.

  • Researchers from institutions with signed Data Use Agreements can begin using the Researcher Workbench.

  • Researchers can create workspaces within the Workbench to create and analyze cohorts of large numbers of de-identified data sets and access genomic data to look for genomic markers.

  • Enrollment in All of Us is still underway, so the data is not yet complete, but will grow richer as participation grows (All of Us aims to engage a cohort of 1 million or more!)

  • UAB has a signed DUA, so any UAB researcher can access the Workbench beta site at this time.

Click here to learn more and access the recent CCTS training and slide deck on the Researcher Workbench beta. You can also explore additional tutorials here.

Mining the Genome - Issue 1

Mining the Genome - Issue 1

An exceptional amount of genomics research activity is underway both locally and nationally, and this column will share new developments and possible implications that will hopefully result in more opportunities for researchers to connect ideas and efforts. Each month, the CCTS will share a conversation with the director of CCTS Genomic Medicine, Bruce Korf, MD, PhD, Wayne H. and Sara Crews Finley Endowed Chair in Medical Genetics, Associate Dean for Genomic Medicine at UAB, and the Chief Genomics Officer for UAB Medicine. Dr. Korf will be providing updates on an array of genomics-related topics and at the end of each column will provide guidance on how you can connect further on that topic.

Let’s kick off this series by establishing a foundation, some genomics groundwork, courtesy of Dr. Korf.

CCTS: What is the overall goal in genomic medicine, from a ‘big picture’ perspective?

Korf: People have been excited about genomics opportunities since the human genome sequence was deciphered, which was now about 17 years ago. But what has become clear is that having the sequence in hand doesn’t automatically translate into better patient care. There’s a lot that has to be done to take that information and develop the systems needed to apply it to patient care, to validate it and demonstrate that it is effective and safe to use. It has therefore taken a fair amount of time to reach this point, where we are now seeing research that is used in routine practice.

From the perspective of an academic medical center, I think there are two things critical for us to keep in mind. We want to provide the best access to cutting edge care that we can—as genomic medicine-related technologies become available and are demonstrated to be effective, we want to make sure our patients have access. But we must also do the work to demonstrate that these approaches have clinical utility. It isn’t just our job to read the book of genomic medicine and apply it to our patients, but to actually write the book.

CCTS: What is genomic medicine?

Korf: Genomics is the study of the entire human genome, the entire complement of genetic material in each of our cells. We have altogether 6 billion base pair of DNA and these encode some 22,000 genes and all of the regulatory processes that turn those genes on or off in the right time and the right place. Genomics really amounts to studying large collections of genetic elements, both genes and control processes to try and put them together into an understanding of how they are important in regulating cell processes, and ultimately contributing to health and disease.

Genetics, in contrast, usually focuses on one gene at a time, and how it is passed from generation to generation and how it functions in the cell, so with genomics we are looking at genes much more globally or collectively. Metaphorically, think of genetics as a book that describes a complicated cellular process and think of genomics as a library of where all of those books are collected.

The concept of genomic medicine is using genomic information to make decisions to either prevent, diagnose, or treat disease. Some of it happens at a at a population level, trying to identify individuals at risk and using that information to try and prevent them from developing disease. Some of it is in achieving a more precise diagnosis in an individual who has symptoms of disease. And finally, genomics also comes into use to identify and guide treatment, and to be sure that treatments being used are used optimally to maximize benefit and minimize side effects.

What initiatives and research developments will Dr. Korf be sharing over the coming months?

Since the genomics landscape is so vast, Korf organizes genomics research into three arenas: rare diseases, common diseases, and cancer, and then conceptualizes each of those into three parts: prevention, diagnosis, and treatment. Korf will use this columns to talk about that entire ‘matrix’ of the genomics world, including work surrounding:

  • The Undiagnosed Diseases Program, which has a 30% success rate in providing a diagnosis for patients who have had great difficulty in receiving a diagnosis

  • The role of genomics in customized cancer therapies

  • The Alabama Genomic Health Initiative, testing Alabamians for the presence of specific genetic variants that may predict the development of serious medical conditions that can be prevented or treated if the diagnosis is made early

  • The All of Us Research Program, an NIH-sponsored initiative to enroll 1 million people to sequence their genomes and collect electronic health record information

  • The eMERGE Consortium, which has a goal to develop polygenic risk scores to identify people at unusually higher risks of disease and use that to institute effective treatments

  • Advancements in Maternal Fetal Medicine preconception counseling and carrier testing

  • The Hugh Kaul Precision Medicine Institute’s work to understand the underlying cause of disease at a genetic level in order to select therapies

  • Developments in pharmacogenetic testing

  • The Center for Precision Animal Models (C-PAM), which is taking genomic variance and developing various animal models that can be used to further study how those gene variants influence disease and treatment.