Professor Russ Corbett-Detig and his Ph.D. student Alex Kramer look at the phylogenetic tree of COVID-19 on UShER, their online tool for pathogen tracking, which the research team will now expand to trace other pathogens. Image credit: screenshot of video produced by Cold Water Chapel.
October 28, 2024
By Emily Cerf
To be better prepared for public health crises like the COVID-19 pandemic, UC Santa Cruz Professor of Biomolecular Engineering Russ Corbett-Detig and his lab are building online tools to track the ongoing genomic evolution of pathogens.
Now, the Centers for Disease Control and Prevention (CDC) has awarded Corbett-Detig and his team at the UCSC Genomics Institute a two-year, $2.52 million contract to continue their work tracking the COVID-19 virus’s evolution and expand their software tools to track other pathogens. The group will also further develop their software tool called UShER, an ever-growing phylogenetic tree that diagrams the evolution of the COVID-19 globally, to make it accessible for more public health groups.
“Russ’s team has proved that they can rapidly develop genomics tools to help with emerging public health challenges,” said Lauren Linton, executive director of the Genomics Institute. “As the Genomics Institute deepens its commitment to impacting human health, we value this continued partnership with the CDC as we expand to address new pathogens. This will have a huge impact on how scientists and public health officials monitor and respond to disease-causing pathogens in real time.”
Co-investigators on the CDC contract include UCSC Bioinformatics Programmer Angie Hinrichs, unofficially nicknamed “the keeper of the [COVID-19] tree,” UCSC Senior Informatician Marc Perry, and UC San Diego Assistant Professor Yatish Turahkia, who wrote the UShER software while he was a postdoctoral scholar in Corbett-Detig’s lab. Several graduate students in Corbett-Detig’s lab will also participate in this project.
“It’s great that academics responded really quickly to the pandemic and did a lot of important innovation,” said Corbett-Detig, who is the associate director of pathogen genomics at the UC Santa Cruz Genomics Institute. “But if we want sustained communities that are able to use these tools, then we really need to get them into the hands of public health practitioners, so we are not just leaning back on rapid academic development again in the face of another crisis.”
The UShER platform has been so successful because early in the pandemic it was the only tool of its kind. The team of researchers behind it were able to identify and solve for a crucial need — that the public health community needed a scalable platform to analyze what became millions of COVID-19 samples being gathered around the world in order to trace and understand the disease’s evolution.
Since then, Corbett-Detig and his team have created tools for the diseases RSV and Mpox, and are working on tools for dengue, influenza, H5N1 (known colloquially as bird flu), and tuberculosis, among others. UShER is also now one of the main tools for tracking COVID-19 evolution worldwide.
Because of the diversity of all global pathogens, however, it is inefficient for Corbett-Detig and his team to create a version of their software pipeline for every individual disease. The new contract will allow them to create a generalized version that can be adapted by scientists and public health officials who study and are experts in a particular pathogen. The researchers are actively looking to connect with more groups studying particular diseases to collaborate and get feedback on their work.
“I’m thrilled that we’ll be able to make it easy to apply UShER tools to new disease-causing viruses and bacteria,” Hinrichs said.
This approach will make this critical public health technology more available and accessible to scientists and healthcare professionals who do not have the extensive bioinformatics training needed to create and run these software tools.
“Where the next explosion of growth for the genomics field will be is getting the products of genomics — the analysis and interpretation of genomics data — into the hands of non-experts,” Corbett-Detig said. “There’s a lot of people that might be trained epidemiologists, for example, but they’re not also trained as bioinformaticians. They need to be able to use the tools but also interpret and trust the output enough to make a real public health decision.”
The tools that the team is building use what they call an “online analysis” approach, which allows researchers and public health officials to build and continuously add to an ever-growing tree of evolution of a virus. This is much more efficient in comparison to traditional “de novo” phylogenetics, which requires making a whole new tree every time there is a new virus sample.
“The very nature of an evolving pathogen is that you will constantly be accumulating new samples,” Corbett-Detig said. “It is very convenient, and better in a lot of ways, to just be able to slot samples into what I already know, rather than starting from scratch every time.”
Using the UShER platform creates a shared language for data structures and data objects that, with buy-in from the public health community, creates a consistent coordinate system for tracking the evolution of a pathogen.
The project team will also be developing methods to make designating lineages automatic rather than manual, in order to have more consistent systems for this naming process. Having a consistent set of criteria for identifying new lineages — take COVID-19’s Omicron lineage for example — will improve public health conversations around virus evolution.
“As soon as a new variant becomes important, it will already have a name, because we already picked it out — we’ll have a system for talking about these things built out,” Corbett-Detig said. “It’s something we’re really excited about.”
The researchers will also build in recombination detection, a process for determining that a new strain is the result of the hybridization of two existing, genetically distinct strains.This can be important information for public health officials seeking to understand potential health threats in their communities.
Corbett-Detig and his group are also working on an ongoing basis with the California Department of Public Health to layer California-specific elements on top of the tools to be used in state and local contexts.