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UTSW lab identifies COVID-19 variants in North Texas

Researchers developed a process for delivering quick and accurate analysis of SARS-CoV-2 variants, allowing scientists to track the variant landscape over time

covid-variant-sequencing-header
Jeffrey SoRelle, M.D., developed a genotyping test that is used to identify COVID-19 variants.

As 2021 began, the U.K.-originating Alpha variant of SARS-CoV-2 – the virus that causes COVID-19 – was the only significant variant circulating in the U.S. Since then, the World Health Organization has identified at least 11 important variants, different strains that arose through mutations to the original Wuhan strain’s genetic code. These aren’t just an academic curiosity, explained Jeffrey SoRelle, M.D., Assistant Professor of Pathology: Variants that stick around represent an evolutionary success, a way for the virus to more fruitfully spread and potentially produce a more severe infection.

The hunt for COVID-19 variants

At UT Southwestern, research by Jeffrey SoRelle, M.D., and colleagues in the Eugene McDermott Center for Human Growth and Development’s Next Generation Sequencing Core shows how the COVID-19 virus is changing in North Texas. Specifically, it indicates which strains of the virus are moving through the region to help policymakers and public health authorities respond to and fight the pandemic.

To identify and track variants in North Texas, Dr. SoRelle partnered over the past year with Helen Hobbs, M.D., Professor of Internal Medicine and Molecular Genetics and an Investigator of the Howard Hughes Medical Institute. Combining a rapid, focused PCR-based test generated in the Once Upon a Time Human Genomics Center and genotyping test that Dr. SoRelle developed in the McDermott Next-Generation Sequencing Core, part of the Eugene McDermott Center for Human Growth and Development that Dr. Hobbs directs, these efforts have provided a wealth of data to show how SARS-CoV-2 has shifted and changed over time.

Helen Hobbs
Helen Hobbs, M.D., is working with Dr. SoRelle to study and track COVID-19 variants in North Texas.

“Our combined work toward tracking variants has allowed us to follow in real time the changes in the viral strains causing disease in our own community,” Dr. Hobbs said.

Tracking variants involves identifying differences in the nearly 30,000 nucleotides, or individual units, that make up the SARS-CoV-2 genome. Rather than starting with reading the entire sequence, a process that takes about a week and a half, Dr. SoRelle’s genotyping method focuses initially on eight “hotspots” for mutation – areas of the genome that have proved rife for genetic changes over the course of the pandemic.

Sequencing
COVID-positive test samples are sent to a high-throughput lab in the Department of Pathology, where Dr. SoRelle genotypes it – a process that takes just six hours.

Dr. SoRelle began developing his test in January 2021, soon after the Alpha variant first spread to the U.S. from the United Kingdom, honing and perfecting his technique over the next several months. Since April 2021, every sample from patients within the UTSW system who tested positive for COVID-19 has been sent to the high-throughput COVID-19 lab in the Department of Pathology, where Dr. SoRelle genotypes it – a process that takes just six hours. Then, to verify his results and offer insight on more subtle changes in the sequence of the genome of the virus, Dr. Hobbs and her colleagues run the samples through the lengthier whole-genome sequencing process. The bioinformatics group in the McDermott Center then uses machine learning to digest this abundance of data, assigning a “lineage” to each specimen that signifies its variant or identifying new changes that could suggest a potentially novel variant.

Over the past year, the team has seen the prevalence of variants rise and fall, including the exponential spread of the Delta variant in recent months, and at least one case of the Omicron variant recently confirmed by the Texas Department of State Health Services. “Through the data we generated, we were able to see the Delta surge coming before it happened,” Dr. SoRelle said.

This data, which the team compiles into a weekly report, has proved extraordinarily useful to UTSW leadership, North Texas businesses, and public health departments as a nearly real-time read of variant trends and for developing forecasting models. Dr. SoRelle said he hopes his genotyping method might eventually be useful for research in public health labs, where it would vastly reduce the time it takes to receive variant results from weeks to hours and shrink costs to about a tenth of the current cost of $200 to $300 per sample.

“A major takeaway from our work is the importance of continuing to track variants over time, because we’ll never be sure what we see in the future,” Dr. SoRelle said. “The more we track, the more we learn.”

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