Genomics Rooftop Mixer: Mapping Gene Isoforms to Improve Treatment
At the University of California, Santa Cruz, the Brooks Lab is transforming how scientists understand cancer genetics through a powerful computational tool called FLAIR—Full-Length Alternative Isoform analysis of RNA. Developed under the leadership of Professor Angela Brooks, FLAIR allows researchers to map and analyze gene isoforms—different versions of genes created when RNA molecules are spliced in multiple ways from the same DNA sequence.
While most cancer research focuses on identifying DNA mutations, it often overlooks the isoforms that those genes produce. Nearly all human genes (over 95%) can generate multiple isoforms, and these subtle variations may determine how cancers grow, respond to therapy, or develop drug resistance. By revealing this hidden layer of complexity, FLAIR gives scientists a clearer view of how cancer truly operates.
FLAIR takes advantage of cutting-edge long-read RNA sequencing technology, which captures entire RNA molecules instead of short fragments. This enables the tool to distinguish between different isoforms with precision, mapping how each version of a gene is expressed in healthy versus cancerous tissue. Brooks and her team use this capability to understand why targeted cancer treatments sometimes fail.
In collaboration with Alice Berger’s lab at the Fred Hutchinson Cancer Center in Seattle, the Brooks Lab is applying FLAIR to lung cancer samples, including those from treatment-resistant patients. Their goal is to uncover which gene isoforms are active in resistant cancers and how those differences might explain why some therapies lose effectiveness over time.
This research marks one of the most comprehensive efforts yet to connect isoform expression with cancer behavior. By integrating FLAIR’s isoform maps with clinical data—such as patient responses to drugs—the team hopes to identify new biomarkers that can predict resistance and guide more personalized treatments.
The data generated through FLAIR will be made available to the global research community via the UCSC Xena Browser, offering scientists a new resource for exploring the interplay between RNA isoforms and cancer genetics.
By illuminating the genetic “fine print” often missed in traditional studies, FLAIR is helping to rewrite the story of cancer research—pushing precision medicine closer to truly individualized care.
Angela Brooks will be joining us at Santa Cruz Works x UCSC Genomics Rooftop Mixer, Tuesday, October 28th for a night of networking and a series of dynamic lightning talks from leading researchers, showcasing the latest advancements and disruptive technologies in the field.
