TGen-USC team develops LumosVar, a new tool in the field of precision medicine
Precision medicine in oncology is based on identifying mutations that turn healthy cells into tumor cells, while taking into account individual differences in a patient’s genes, environment, and lifestyle. When possible, researchers and clinicians sift through a patient’s genome to identify mutations and then use that information to find pre-existing therapies known to have success against those particular mutations.
Drawing on the fictional world of Harry Potter, researchers at TGen and the University of Southern California (USC) developed LumosVar, a computational tool that helps identify genetic variants that could contribute to cancer while adding a bit of clarity to the field of precision medicine.
There are two main approaches to identify mutations. Ideally, the genomic signatures in a patient’s tumor cells, and the patient’s normal tissue cells, are both sequenced. By comparing
the two, researchers can identify mutations that may be specific to that patient’s tumor.
However, in assembling research, collecting normal tissue is not always possible. In these cases tumor-only sequencing is an alternative.
Findings from a recent TGen-USC study published in the scientific journal BMC Medical Genomics, details how scientists might identify genetic variants in the tumor that might cause cancer.
“It is very difficult to identify a somatic, or potentially cancer-causing, variant when you don’t have a germline, or normal tissue, sample,” said Dr. Rebecca Halperin (pictured), a TGen Assistant Research Professor and one of the study’s lead authors.
To assist researchers in sorting false positives from those mutations that might actually cause cancer, TGen and USC researchers devised LumosVar, a Harry Potter reference to Lumos (light) in the story’s magic spells, and Var for genetic variance.
LumosVar is essentially a tool to light up the genome’s potentially cancer-causing genetic mutations.
“The approach that we present relies on the fact that most solid tumor samples are actually a mixture of tumor cells and normal cells. We rely on the fact that the normal cells don’t have the somatic mutations, and that’s what allows us to tell the difference between somatic variants and the germline variants,” said Dr. Halperin, one of the co-creators of LumosVar.
The TGen-USC team has offered LumosVar as an open-source tool for any researcher to use in searching for potentially cancer-causing mutations.
The research team set out to evaluate the benefit and limitations of leveraging allele frequencies to distinguish somatic and germline variants in unmatched tumor samples, and in the process developed a tool that is now freely available to the greater research community.
The study — funded by The Ben & Catherine Ivy Foundation and by the Multiple Myeloma Research Foundation — predicts that, as the cost of high-depth sequencing continues to decline, the sensitivity of tools like LumosVar will continue to improve.
