Advances in translational genetics unlocked by Bio-Rad technologies to be presented at ASHG 2019

Reviewed by James Ives, M.Psych. (Editor)Oct 15 2019

Scientists will present 24 abstracts and three talks, highlighting research driven in part by Bio-Rad Laboratories' Droplet Digital PCR (ddPCR) and single-cell ATAC-Seq (scATAC-Seq) technologies, at the 2019 American Society of Human Genetics (ASHG) Annual Meeting in Houston, October 15-19. The research presented shows that sensitive and reliable methods such as Bio-Rad's scATAC-Seq and ddPCR provide researchers a way to study epigenetic regulation at scale and improve the detection of previously identified biomarkers.

Below are highlights of two of the presentations that demonstrate the use of Bio-Rad's droplet-based technologies in epigenetic discovery research and in identifying biomarkers for toxin exposure.

Single-cell epigenomic mapping at unprecedented scale using Bio-Rad's scATAC-Seq Solution

Recent technical advances have facilitated the mapping of epigenomes at single-cell resolution. However, the throughput and quality of these methods have limited their ability to be scaled for large experiments.

To address this problem, Ronald Lebofsky, PhD, of Bio-Rad, and Caleb Lareau of Harvard University will describe a high-quality droplet microfluidics-based method for single-cell profiling of chromatin accessibility. In their research, they employed a droplet single-cell assay for transposase-accessible chromatin using sequencing (dscATAC-Seq) to discover regulatory elements in 46,653 cells in the adult mouse brain.

The researchers increased the throughput of Bio-Rad's ddSEQ Single-Cell Isolator platform by combining it with a barcoded transposase, enabling a more than tenfold increase in cells they could assay. This allowed them to measure chromatin accessibility across 136,463 resting and stimulated human bone marrow-derived cells and to reveal changes in epigenetic regulation across different cell types and under different environmental conditions at single-cell resolution. Altogether, they described a total of over a half-million single-cell profiles, demonstrating the scalability and flexibility of the droplet-based ddSEQ platform.

"By leveraging Bio-Rad's technological platforms to increase the throughput of epigenomic mapping, we can explore variations between cell types of tissues at unprecedented scale and resolution," said Lebofsky.

This talk will take place on Thursday, October 17, 12:45-2 PM at the Marriott Marquis Houston Meyerland AB, Level 3.

First rapid test for assessing cigarette smoking and chronic alcohol consumption

Smoking and alcoholism are the first and fourth leading preventable causes of death in the U.S., respectively. To date, no objective tests have been available to measure these behaviors or to confirm patient-reported use. Robert Philibert, MD, PhD, and CEO of Behavioral Diagnostics, LLC used ddPCR technology to develop the first epigenetic test for quantifying chronic tobacco and alcohol use.

Philibert and his team had previously identified methylation biomarkers for drinking and smoking using genome-wide analysis methods. At ASHG, they will present the findings of a ddPCR test that was used to analyze either whole blood or saliva from 233 smokers and 143 heavy drinkers. The scientists showed that ddPCR technology can be used to quantify the concentration of a methylation biomarker that correlates with daily cigarette consumption. Similarly, he found that demethylation at four other sites correlated with heavy alcohol consumption in a dose-dependent manner. If validated, the test could be useful to clinicians and researchers in assessing and monitoring patients in a variety of wellness programs.

We used ddPCR technology for this test because precision and accuracy in clinical settings is paramount. Getting this kind of test wrong can be harmful to patients. Droplet Digital PCR technology is highly scalable. And unlike qPCR, it doesn't rely on reference genes, which makes it more reliable."

Robert Philibert, MD, PhD, and CEO of Behavioral Diagnostics

Philibert plans to seek approval from the U.S. Food and Drug Administration to use both tests in the clinic.

This poster (abstract 3298) will be presented on Thursday, October 18, 3-4 PM.

On Thursday, October 17, Bio-Rad will host two Exhibitor Education Events reporting novel research applications for scATAC-Seq:

7:15-8:45 AM, Hilton Americas Houston Lanier Ballroom J, Level 4 - Andrea Cosarizza, MD, PhD, of the University of Modena, will give a talk titled "Monitoring Changes to the Immune System during Immunological Treatment of Cancer Using High-Speed Cell Sorting and Single-Cell RNA-Seq."

3:15-4 PM, CoLab Theater 1 #345, Exhibit Hall - Ethan A. Winkler, MD, PhD, of the University of California, San Francisco, and Pranav Patel, PhD, of Bio-Rad, will give a talk titled "Development of RNA-Seq-Based Endovascular Biopsy for Brain Arteriovenous Malformations."

For more details about these talks visit the ASHG meeting schedule.

For demonstrations of the QX200 AutoDG ddPCR System, ddSEQ, and other Bio-Rad instruments, visit booth #530. To learn more about Bio-Rad's ddPCR technology that will be presented at ASHG, visit bio-rad.com/digitalPCR.

BIO-RAD, DDPCR, and DROPLET DIGITAL PCR are trademarks of Bio-Rad Laboratories, Inc. in certain jurisdictions. All trademarks used herein are the property of their respective owner.